Metabolism and disposition kinetics of nicotine

Pharmacological Reviews

Volumn 57, Issue 1, 2005, Pages 79-115

  Hukkanen, Janne ^b   Jacob III, Peyton ^b   Benowitz, Neal L ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b NONE

Author keywords

[No Author keywords available]

Indexed keywords

2 METHYL 3 (2 PYRROLIDINYLMETHOXY)PYRIDINE; 3 (2 AZETIDINYLMETHOXY)PYRIDINE; 3 (2,4 DIMETHOXYBENZYLIDENE)ANABASEINE; 3 ETHYNYL 5 (1 METHYL 2 PYRROLIDINYL)PYRIDINE; 3 ETHYNYL 5 (1 METHYL 2 PYRROLIDINYL)PYRIDINE FUMARATE; 3 METHYL 5 (1 METHYL 2 PYRROLIDINYL)ISOXAZOLE; 3' HYDROXYCOTININE; 5 (2 AZETIDINYLMETHOXY) 2 CHLOROPYRIDINE; ALDEHYDE OXIDASE; ALKALOID DERIVATIVE; ANABASINE; CARBAMAZEPINE; CLONAZEPAM; COTININE; COUMARIN; CYTOCHROME P450 2A6; DEXAMETHASONE; DIMETHYLANILINE MONOOXYGENASE; EPIBATIDINE; GLUCURONOSYLTRANSFERASE; METANICOTINE; METHYLTRANSFERASE; N METHYL 4 (3 PYRIDINYL) 3 BUTENAMINE; NICOTINE; NORNICOTINE; PHENOBARBITAL; PILOCARPINE; PYRAZOLE; RIFAMPICIN; UNCLASSIFIED DRUG; UNINDEXED DRUG;

CLINICAL TRIAL; DIET; DRUG ABSORPTION; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG EXCRETION; DRUG GLUCURONIDATION; DRUG METABOLISM; ENZYME ACTIVITY; ENZYME POLYMORPHISM; ENZYME REGULATION; ETHNIC DIFFERENCE; GENE FREQUENCY; GENETIC VARIABILITY; HUMAN; INTOXICATION; KIDNEY DISEASE; LIVER DISEASE; LOZENGE; NICOTINE REPLACEMENT THERAPY; NONHUMAN; PHENOTYPE; PREGNANCY; PRIORITY JOURNAL; RACE DIFFERENCE; REVIEW; SEX DIFFERENCE; SMOKING; SMOKING CESSATION; SPECIES DIFFERENCE; TOBACCO; URINARY EXCRETION;

ABSORPTION; ANIMALS; ARYL HYDROCARBON HYDROXYLASES; BIOLOGICAL AVAILABILITY; FEMALE; GANGLIONIC STIMULANTS; HUMANS; LIVER; MALE; METABOLIC CLEARANCE RATE; MIXED FUNCTION OXYGENASES; NICOTINE; SMOKING; TISSUE DISTRIBUTION;

EID: 14144253640     PISSN: 00316997     EISSN: None     Source Type: Journal    
DOI: 10.1124/pr.57.1.3     Document Type: Review

References (456)

1. Abu-Bakar A, Satarug S, Marks GC, Lang MA, and Moore MR (2004) Acute cadmium chloride administration induces hepatic and renal CYP2A5 mRNA, protein and activity in the mouse: involvement of transcription factor NRF2. Toxicol Lett 148:199-210.
2. Ahijevych K and Gillespie J (1997) Nicotine dependence and smoking topography among black and white women. Res Nurs Health 20:505-514.
3. Ahijevych KL, Tyndale RF, Dhatt RK, Weed HG, and Browning KK (2002) Factors influencing cotinine half-life during smoking abstinence in African American and Caucasian women. Nicotine Tob Res 4:423-431.
4. Aislaitner G, Li Y, and Gorrod JW (1992) In vitro studies on (-)-nornicotine. Med Sci Res 20:897-899.
5. Albert C, Vallee M, Beaudry G, Belanger A, and Hum DW (1999) The monkey and human uridine diphosphate-glucuronosyltransferase UGT1A9, expressed in steroid target tissues, are estrogen-conjugating enzymes. Endocrinology 140:3292-3302.
6. 3H]ABT-418: a novel cholinergic channel ligand. J Pharmacol Exp Ther 273:1434-1441.
7. Andersson G, Vala EK, and Curvall M (1997) The influence of cigarette consumption and smoking machine yields of tar and nicotine on the nicotine uptake and oral mucosal lesions in smokers. J Oral Pathol Med 26:117-123.
8. Ariyoshi N, Miyamoto M, Umetsu Y, Kunitoh H, Dosaka-Akita H, Sawamura Y, Yokota J, Nemoto N, Sato K, and Kamataki T (2002) Genetic polymorphism of CYP2A6 gene and tobacco-induced lung cancer risk in male smokers. Cancer Epidemiol Biomarkers Prev 11:890-894.
9. Ariyoshi N, Sawamura Y, and Kamataki T (2001) A novel single nucleotide polymorphism altering stability and activity of CYP2A6. Biochem Biophys Res Commun 281:810-814.
10. Ariyoshi N, Takahashi Y, Miyamoto M, Umetsu Y, Daigo S, Tateishi T, Kobayashi S, Mizorogi Y, Loriot MA, Stucker I, et al. (2000) Structural characterization of a new variant of the CYP2A6 gene (CYP2A6*1B) apparently diagnosed as heterozygotes of CYP2A6*1A and CYP2A6*4C. Pharmacogenetics 10:687-693.
11. Armitage A, Dollery C, Houseman T, Kohner E, Lewis PJ, and Turner D (1978) Absorption of nicotine from small cigars. Clin Pharmacol Ther 23:143-151.
12. Armitage AK, Dollery CT, George CF, Houseman TH, Lewis PJ, and Turner DM (1975) Absorption and metabolism of nicotine from cigarettes. Br Med J 4:313-316.
13. Armstrong DW, Wang X, and Ercal N (1998) Enantiomeric composition of nicotine in smokeless tobacco, medicinal products and commercial reagents. Chirality 10:587-591.
14. Armstrong DW, Wang X, Lee J-T, and Liu Y-S (1999) Enantiomeric composition of nornicotine, anatabine and anabasine in tobacco. Chirality 11:82-84.
15. Asikainen A, Tarhanen J, Poso A, Pasanen M, Alhava E, and Juvonen RO (2003) Predictive value of comparative molecular field analysis modelling of naphthalene inhibition of human CYP2A6 and mouse CYP2A5 enzymes. Toxicol In Vitro 17:449-455.
16. Ayesh R, Al-Waiz M, Crothers J, Cholerton S, Mitchell SC, Idle JR, and Smith RL (1988) Deficient nicotine N-oxidation in two sisters with trimethylaminuria. Br J Clin Pharmacol 25:664P-665P.
17. Azuma R, Komuro M, Korsch BH, Andre JC, Onnagawa O, Black SR, and Mathews JM (1999) Metabolism and disposition of GTS-21, a novel drug for Alzheimer's disease. Xenobiotica 29:747-762.
18. Bailey DG, Spence JD, Munoz C, and Arnold JM (1991) Interaction of citrus juices with felodipine and nifedipine. Lancet 337:268-269.
19. Baker JR, Satarug S, Reilly PE, Edwards RJ, Ariyoshi N, Kamataki T, Moore MR, and Williams DJ (2001) Relationships between non-occupational cadmium exposure and expression of nine cytochrome P450 forms in human liver and kidney cortex samples. Biochem Pharmacol 62:713-721.
20. Balabanova S, Buhler G, Schneider E, Boschek HJ, and Schneitler H (1992) Nicotine excretion by the apocrine and eccrine sweat in smokers and passive smokers. Hautarzt 43:73-76.
21. Balabanova S and Krupienski M (1995) Detection of nicotine in eccrine sweat after stimulation of sweat glands during nicotine withdrawal. Hautarzt 46:255-258.
22. Balabanova S and Schneider E (1990) Detection of drugs in sweat. Beitr Gerichtl Med 48:45-49.
23. Balfour DJ (2002) The neurobiology of tobacco dependence: a commentary. Respiration 69:7-11.
24. Bannon AW, Decker MW, Holladay MW, Curzon P, Donnelly-Roberts D, Puttfarcken PS, Bitner RS, Diaz A, Dickenson AH, Porsolt RD, et al. (1998) Broad-spectrum, non-opioid analgesic activity by selective modulation of neuronal nicotinic acetylcholine receptors. Science (Wash DC) 279:77-81.
25. Bao Z, Su T, Ding X, and Hong J-Y (2000) Metabolism of nicotine and cotinine by human cytochrome P450 2A13 (CYP2A13), in 13th International Symposium on Microsomes and Drug Oxidations, July 10-14, 2000, Stresa, Italy (Abstract 137).
26. Baranowski J, Pochopien G, and Baranowska I (1998) Determination of nicotine, cotinine and caffeine in meconium using high-performance liquid chromatography. J Chromatogr B Biomed Sci Appl 707:317-321.
27. Beckett AH, Gorrod JW, and Jenner P (1970) Absorption of (-)-nicotine-1-N-oxide in man and its reduction in the gastrointestinal tract. J Pharm Pharmacol 22:722-723.
28. Beckett AH, Gorrod JW, and Jenner P (1972) A possible relation between pKa 1 and lipid solubility and the amounts excreted in urine of some tobacco alkaloids given to man. J Pharm Pharmacol 24:115-120.
29. Beckett AH and Sheikh AH (1973) Proceedings: In vitro metabolic N-oxidation of the minor tobacco alkaloids, (-)methylanabasine and (-)anabasine to yield a hydroxylamine and a nitrone in long and liver homogenates. J Pharm Pharmacol 25 (Suppl):171P.
30. Beedham C, Miceli JJ, and Obach RS (2003) Ziprasidone metabolism, aldehyde oxidase and clinical implications. J Clin Psychopharmacol 23:229-232.
31. Bencherif M, Lovette ME, Fowler KW, Arlington S, Reeves L, Caldwell WS, and Lippiello PM (1996) RJR-2403: a nicotinic agonist with CNS selectivity I. In vitro characterization. J Pharmacol Exp Ther 279:1413-1421.
32. Bendayan R, Sullivan JT, Shaw C, Frecker RC, and Sellers EM (1990) Effect of cimetidine and ranitidine on the hepatic and renal elimination of nicotine in humans. Eur J Clin Pharmacol 38:165-169.
33. Benowitz NL (1990) Clinical pharmacology of inhaled drugs of abuse: implications in understanding nicotine dependence. NIDA Res Monogr 99:12-29.
34. Benowitz NL (1993) Nicotine replacement therapy. What has been accomplished - can we do better? Drugs 45:157-170.
35. Benowitz NL (1995) Clinical pharmacology of transdermal nicotine. Eur J Pharm Biopharm 41:168-174.
36. Benowitz NL (1996a) Cotinine as a biomarker of environmental tobacco smoke exposure. Epidemiol Rev 18:188-204.
37. Benowitz NL (1996b) Pharmacology of nicotine: addiction and therapeutics. Annu Rev Pharmacol Toxicol 36:597-613.
38. Benowitz NL (1999) Nicotine addiction. Prim Care 26:611-631.
39. Benowitz NL, Griffin C, and Tyndale R (2001) Deficient C-oxidation of nicotine continued. Clin Pharmacol Ther 70:567.
40. Benowitz NL, Hall SM, Herning RI, Jacob P 3rd, Jones RT, and Osman AL (1983a) Smokers of low-yield cigarettes do not consume less nicotine. N Engl J Med 309:139-142.
41. Benowitz NL, Herrera B, and Jacob P 3rd (2004a) Mentholated cigarette smoking inhibits nicotine metabolism. J Pharmacol Exp Ther 310:1208-1215.
42. Benowitz NL and Jacob P 3rd (1984) Daily intake of nicotine during cigarette smoking. Clin Pharmacol Ther 35:499-504.
43. Benowitz NL and Jacob P 3rd (1985) Nicotine renal excretion rate influences nicotine intake during cigarette smoking. J Pharmacol Exp Ther 234:153-155.
44. Benowitz NL and Jacob P 3rd (1993) Nicotine and cotinine elimination pharmacokinetics in smokers and nonsmokers. Clin Pharmacol Ther 53:316-323.
45. Benowitz NL and Jacob P 3rd (1994) Metabolism of nicotine to cotinine studied by a dual stable isotope method. Clin Pharmacol Ther 56:483-493.
46. Benowitz NL and Jacob P 3rd (1998) Pharmacokinetics and metabolism of nicotine and related alkaloids, in Neuronal Nicotinic Receptors: Pharmacology and Therapeutic Opportunities (Arneric SP and Brioni JD eds) pp 211-234, Wiley-Liss, Inc., New York.
47. Benowitz NL and Jacob P 3rd (2000) Effects of cigarette smoking and carbon monoxide on nicotine and cotinine metabolism. Clin Pharmacol Ther 67:653-659.
48. Benowitz NL and Jacob P 3rd (2001) Trans-3′-hydroxycotinine: disposition kinetics, effects and plasma levels during cigarette smoking. Br J Clin Pharmacol 51:53-59.
49. Benowitz NL, Jacob P 3rd, Denaro C, and Jenkins R (1991) Stable isotope studies of nicotine kinetics and bioavailability. Clin Pharmacol Ther 49:270-277.
50. Benowitz NL, Jacob P 3rd, Fong I, and Gupta S (1994) Nicotine metabolic profile in man: comparison of cigarette smoking and transdermal nicotine. J Pharmacol Exp Ther 268:296-303.
51. Benowitz NL, Jacob P 3rd, Jones RT, and Rosenberg J (1982a) Interindividual variability in the metabolism and cardiovascular effects of nicotine in man. J Pharmacol Exp Ther 221:368-372.
52. Benowitz NL, Jacob P 3rd, and Perez-Stable E (1996) CYP2D6 phenotype and the metabolism of nicotine and cotinine. Pharmacogenetics 6:239-242.
53. Benowitz NL, Jacob P 3rd, and Sachs DP (1995) Deficient C-oxidation of nicotine. Clin Pharmacol Ther 57:590-594.
54. Benowitz NL, Jacob P 3rd, and Savanapridi C (1987) Determinants of nicotine intake while chewing nicotine polacrilex gum. Clin Pharmacol Ther 41:467-473.
55. Benowitz NL, Kuyt F, and Jacob P 3rd (1982b) Circadian blood nicotine concentrations during cigarette smoking. Clin Pharmacol Ther 32:758-764.
56. Benowitz NL, Kuyt F, Jacob P 3rd, Jones RT, and Osman AL (1983b) Cotinine disposition and effects. Clin Pharmacol Ther 34:604-611.
57. Benowitz NL, Perez-Stable EJ, Fong I, Modin G, Herrera B, and Jacob P 3rd (1999) Ethnic differences in N-glucuronidation of nicotine and cotinine. J Pharmacol Exp Ther 291:1196-1203.
58. Benowitz NL, Perez-Stable EJ, Herrera B, and Jacob P 3rd (2002a) Slower metabolism and reduced intake of nicotine from cigarette smoking in Chinese-Americans. J Natl Cancer Inst 94:108-115.
59. Benowitz NL, Pomerleau OF, Pomerleau CS, and Jacob P 3rd (2003) Nicotine metabolite ratio as a predictor of cigarette consumption. Nicotine Tob Res 5:621-624.
60. Benowitz NL, Porchet H, and Jacob P 3rd (1990) Pharmacokinetics, metabolism, and phannacodynamics of nicotine, in Nicotine Psychopharmacology: Molecular, Cellular and Behavioral Aspects (Wonnacot S, Russell MAH, and Stolerman IP eds) pp 112-157, Oxford University Press, Oxford.
61. Benowitz NL, Porchet H, Sheiner L, and Jacob P 3rd (1988) Nicotine absorption and cardiovascular effects with smokeless tobacco use: comparison with cigarettes and nicotine gum. Clin Pharmacol Ther 44:23-28.
62. Benowitz NL, Swan GE, Lessov CN, and Jacob P 3rd (2004b) Oral contraceptives induce CYP2A6 activity and accelerate nicotine metabolism (abstract). Clin Pharmacol Ther 75:P36.
63. Benowitz NL, Tyndale H, Jacob P 3rd, and Swan GE (2002b) CYP2A6 polymorphism and nicotine metabolism (Abstract). Clin Pharmacol Ther 71:P41.
64. 3H]nicotine binding sites in human brain. J Neurochem 50:1243-1247.
65. Bergstrom M, Nordberg A, Lunell E, Antoni G, and Langstrom B (1995) Regional deposition of inhaled 11C-nicotine vapor in the human airway as visualized by positron emission tomography. Clin Pharmacol Ther 57:309-317.
66. Berkman CE, Park SB, Wrighton SA, and Cashman JR (1995) In vitro-in vivo correlations of human (S)-nicotine metabolism. Biochem Pharmacol 50:565-570.
67. Bieche I, Girault I, Urbain E, Tozlu S, and Lidereau R (2004) Relationship between intratumoral expression of genes coding for xenobiotic-metabolizing enzymes and benefit from adjuvant tamoxifen in estrogen receptor alpha-positive postmenopausal breast carcinoma. Breast Cancer Res 6:R252-R263.
68. Bolt HM, Roos PH, and Thier R (2003) The cytochrome P-450 isoenzyme CYP2E1 in the biological processing of industrial chemicals: consequences for occupational and environmental medicine. Int Arch Occup Environ Health 76:174-185.
69. Borlak J, Walles M, Levsen K, and Thum T (2003) Verapamil: metabolism in cultures of primary human coronary arterial endothelial cells. Drug Metab Dispos 31:888-891.
70. Bourrie M, Meunier V, Berger Y, and Fabre G (1996) Cytochrome P450 isoform inhibitors as a tool for the investigation of metabolic reactions catalyzed by human liver microsomes. J Pharmacol Exp Ther 277:321-332.
71. Bowman ER and McKennis H Jr (1962) Studies on the metabolism of (-)-cotinine in the human. J Pharmacol Exp Ther 135:306-311.
72. Bowman ER, Turnbull LB, and McKennis H Jr (1959) Metabolism of nicotine in the human and excretion of pyridine compounds by smokers. J Pharmacol Exp Ther 127:92-95.
73. Boyland E and de Kock DH (1966) Nicotine metabolism. Annu Rep Brit Emp Cancer Campaign 44:5.
74. Brandange S and Lindblom L (1979a) The enzyme "aldehyde oxidase" is an iminium oxidase. Reaction with nicotine delta 1′(5′) iminium ion. Biochem Biophys Res Commun 91:991-996.
75. Brandange S and Lindblom L (1979b) Synthesis, structure and stability of nicotine Δ1′(5′) iminium ion, an intermediary metabolite of nicotine. Acta Chem Scand B 33:187-191.
76. 3H]nicotine binding in human postmortem brain. J Pharmacol Exp Ther 282:7-13.
77. Brunnemann KD and Hoffmann D (1974) The pH of tobacco smoke. Fd Cosmet Toxicol 12:115-124.
78. Byrd GD, Chang KM, Greene JM, and deBethizy JD (1992) Evidence for urinary excretion of glucuronide conjugates of nicotine, cotinine and trans-3′-hydroxycotinine in smokers. Drug Metab Dispos 20:192-197.
79. Byrd GD, Davis RA, and Kazemi-Vala E (1995a) Comparison of methods for determining nicotine and its metabolites in urine, in Conference of the Society for Research on Nicotine and Tobacco, Mar 1995, San Diego, CA. Poster 9.
80. Byrd GD, Robinson JH, Caldwell WS, and deBethizy JD (1995b) Comparison of measured and FTC-predicted nicotine uptake in smokers. Psychopharmacology (Berl) 122:95-103.
81. Byrd GD, Uhrig MS, deBethizy JD, Caldwell WS, Crooks PA, Ravard A, and Riggs R (1994) Direct determination of cotinine-N-glucuronide in urine using thermospray liquid chromatography/mass spectrometry. Biol Mass Spectrom 23:103-107.
82. Caldwell WS, Greene JM, Byrd GD, Chang KM, Uhrig MS, deBethizy JD, Crooks PA, Bhatti BS, and Riggs RM (1992) Characterization of the glucuronide conjugate of cotinine: a previously unidentified major metabolite of nicotine in smokers' urine. Chem Res Toxicol 5:280-285.
83. Caporaso NE, Lerman C, Audrain J, Boyd NR, Main D, Issaq HJ, Utermahlan B, Falk RT, and Shields P (2001) Nicotine metabolism and CYP2D6 phenotype in smokers. Cancer Epidemiol Biomarkers Prev 10:261-263.
84. Caraballo HS, Giovino GA, Pechacek TF, Mowery PD, Richter PA, Strauss WJ, Sharp DJ, Eriksen MP, Pirkle JL, and Maurer KR (1998) Racial and ethnic differences in serum cotinine levels of cigarette smokers: Third National Health and Nutrition Examination Survey, 1988-1991. JAMA (J Am Med Assoc) 280:135-139.
85. Carmella SG, Borukhova A, Desai D, and Hecht SS (1997) Evidence for endogenous formation of tobacco-specific nitrosamines in rats treated with tobacco alkaloids and sodium nitrite. Carcinogenesis 18:587-592.
86. Carmella SG, McIntee EJ, Chen M, and Hecht SS (2000) Enantiomeric composition of N′-nitrosonornicotine and N′-nitrosoanatabine in tobacco. Carcinogenesis 21:839-843.
87. Cascorbi I (2003) Pharmacogenetics of cytochrome p4502D6: genetic background and clinical implication. Eur J Clin Investig 33 (Suppl 2):17-22.
88. Cashman JR, Park SB, Yang ZC, Wrighton SA, Jacob P 3rd, and Benowitz NL (1992) Metabolism of nicotine by human liver microsomes: stereoselective formation of trans-nicotine N′-oxide. Chem Res Toxicol 5:639-646.
89. Cashman JR and Zhang J (2002) Interindividual differences of human flavin-containing monooxygenase 3: genetic polymorphisms and functional variation. Drug Metab Dispos 30:1043-1052.
90. Castorena JL, Garriott JC, Barnhardt FE, and Shaw RF (1987) A fatal poisoning from Nicotiana glauca. J Toxicol Clin Toxicol 25:429-435.
91. CDC (Centers for Disease Control) (1993) Smoking cessation during previous year among adults-United States, 1990 and 1991. MMWR Morb Mortal Wkly Rep 42:504-507.
92. Chauret N, Gauthier A, Martin J, and Nicoll-Griffith DA (1997) In vitro comparison of cytochrome P450-mediated metabolic activities in human, dog, cat and horse. Drug Metab Dispos 25:1130-1136.
93. Chen Y, Ferguson SS, Negishi M, and Goldstein JA (2003a) Identification of constitutive androstane receptor and glucocorticoid receptor binding sites in the CYP2C19 promoter. Mol Pharmacol 64:316-324.
94. Chen Y, Liu YQ, Su T, Ren X, Shi L, Liu D, Gu J, Zhang QY, and Ding X (2003b) Immunoblot analysis and immunohistochemical characterization of CYP2A expression in human olfactory mucosa. Biochem Pharmacol 66:1245-1251.
95. Choi JH, Dresler CM, Norton MR, and Strahs KR (2003) Pharmacokinetics of a nicotine polacrilex lozenge. Nicotine Tob Res 5:635-644.
96. Cholerton S, Ayesh R, Idle JR, and Smith RL (1988) The pre-eminence of nicotine N-oxidation and its diminution after carbamizole administration. Br J Clin Pharmacol 26:652P-653P.
97. Christian K, Lang M, Maurel P, and Raffalli-Mathieu F (2004) Interaction of heterogeneous nuclear ribonucleoprotein A1 with cytochrome P450 2A6 mRNA: implications for post-transcriptional regulation of the CYP2A6 gene. Mol Pharmacol 65:1405-1414.
98. Clark MS, Rand MJ, and Vanov S (1965) Comparison of pharmacological activity of nicotine and related alkaloids occurring in cigarette smoke. Arch Int Pharmacodyn Ther 156:363-379.
99. Collier AM, Goldstein GM, Shrewsbury RP, Davis SM, Koch GG, Zhang C-A, Benowitz NL, Lewtas J, and Williams RW (1994) Cotinine elimination and its use as a biomarker in young children involuntarily exposed to environmental tobacco smoke. Indoor Environ 3:353-359.
100. Compton RF, Sandborn WJ, Lawson GM, Sheets AJ, Mays DC, Zins BJ, Tremaine WJ, Lipsky JJ, Mahoney DW, Zinsmeister AR, et al. (1997) A dose-ranging pharmacokinetic study of nicotine tartrate following single-dose delayed-release oral and intravenous administration. Aliment Pharmacol Ther 11:865-874.
101. Cosford ND, Bleicher L, Herbaut A, McCallum JS, Vernier JM, Dawson H, Whitten JP, Adams P, Chavez-Noriega L, Correa LD, et al. (1996) (S)-(-)-5-Ethynyl-3-(1-methyl-2-pyrrolidinyl)pyridine maleate (SIB-1508Y): a novel anti-parkinsonian agent with selectivity for neuronal nicotinic acetylcholine receptors. J Med Chem 39:3235-3237.
102. Court JA, Lloyd S, Thomas N, Piggott MA, Marshall EF, Morris CM, Lamb H, Perry RH, Johnson M, and Perry EK (1998) Dopamine and nicotinic receptor binding and the levels of dopamine and homovanillic acid in human brain related to tobacco use. Neuroscience 87:63-78.
103. Crawford EL, Weaver DA, DeMuth JP, Jackson CM, Khuder SA, Frampton MW, Utell MJ, Thilly WG, and Willey JC (1998) Measurement of cytochrome P450 2A6 and 2E1 gene expression in primary human bronchial epithelial cells. Carcinogenesis 19:1867-1871.
104. Crooks PA and Godin CS (1988) N-Methylation of nicotine enantiomers by human liver cytosol. J Pharm Pharmacol 40:153-154.
105. Curvall M, Kazemi-Vala E, and Englund G (1991) Conjugation pathways in nicotine metabolism, in Effects of Nicotine on Biological Systems (Adlkofer F and Thurau K eds) pp 69-75, Birkhauser Verlag, Basel.
106. Dahlstrom A, Lundell B, Curvall M, and Thapper L (1990) Nicotine and cotinine concentrations in the nursing mother and her infant. Acta Paediatr Scand 79:142-147.
107. Daigo S, Takahashi Y, Fujieda M, Ariyoshi N, Yamazaki H, Koizumi W, Tanabe S, Saigenji K, Nagayama S, Ikeda K, et al. (2002) A novel mutant allele of the CYP2A6 gene (CYP2A6*11) found in a cancer patient who showed poor metabolic phenotype towards tegafur. Pharmacogenetics 12:299-306.
108. Dajani RM, Gorrod JW, and Beckett AH (1975) Reduction in vivo of (minus)-nicotine-1′-N-oxide by germ-free and conventional rats. Biochem Pharmacol 24:648-650.
109. Dalet-Beluche I, Boulenc X, Fabre G, Maurel P, and Bonfils C (1992) Purification of two cytochrome P450 isozymes related to CYP2A and CYP3A gene families from monkey (baboon, Papio papio) liver microsomes. Cross reactivity with human forms. Eur J Biochem 204:641-648.
110. 125I]IPH, an epibatidine analog, binds with high affinity to neuronal nicotinic cholinergic receptors. J Pharmacol Exp Ther 282:445-451.
111. Degawa M, Stern SJ, Martin MV, Guengerich FP, Fu PP, Ilett KF, Kaderlik RK, and Kadlubar FF (1994) Metabolic activation and carcinogen-DNA adduct detection in human larynx. Cancer Res 54:4915-4919.
112. de Leon J, Diaz FJ, Rogers T, Browne D, Dinsmore L, Ghosheh OH, Dwoskin LP, and Crooks PA (2002) Total cotinine in plasma: a stable biomarker for exposure to tobacco smoke. J Clin Psychopharmacol 22:496-501.
113. Dempsey D, Jacob P 3rd, and Benowitz NL (2000) Nicotine metabolism and elimination kinetics in newborns. Clin Pharmacol Ther 67:458-465.
114. Dempsey D, Jacob P 3rd, and Benowitz NL (2002) Accelerated metabolism of nicotine and cotinine in pregnant smokers. J Pharmacol Exp Ther 301:594-598.
115. Dempsey D, Moore C, Deitermann D, Lewis D, Feeley B, and Niedbala RS (1999) The detection of cotinine in hydrolyzed meconium samples. Forensic Sci Int 102:167-171.
116. Dempsey D, Tutka P, Jacob P 3rd, Allen F, Schoedel K, Tyndale RF, and Benowitz NL (2004) Nicotine metabolite ratio as an index of cytochrome P450 2A6 metabolic activity. Clin Pharmacol Ther 76:64-72.
117. Dempsey DA and Benowitz NL (2001) Risks and benefits of nicotine to aid smoking cessation in pregnancy. Drug Safety 24:277-322.
118. Denton TT, Zhang X, and Cashman JR (2004) Nicotine-related alkaloids and metabolites as inhibitors of human cytochrome P-450 2A6. Biochem Pharmacol 67:751-756.
119. Derauf C, Katz AR, and Easa D (2003) Agreement between maternal self-reported ethanol intake and tobacco use during pregnancy and meconium assays for fatty acid ethyl esters and cotinine. Am J Epidemiol 158:705-709.
120. De Schepper PJ, Van Hecken A, Daenens P, and Van Rossum JM (1987) Kinetics of cotinine after oral and intravenous administration to man. Eur J Clin Pharmacol 31:583-588.
121. Domino EF, Hornbach E, and Demana T (1993) The nicotine content of common vegetables. N Engl J Med 329:437.
122. Domino EF, Kadoya C, Matsuoka S, Ni L, and Fedewa KS (2003) Comparative American and Japanese tobacco smoke uptake parameters after overnight tobacco deprivation. Prog Neuropsychopharmacol Biol Psychiatry 27:973-984.
123. Donato MT, Viitala P, Rodriguez-Antona C, Lindfors A, Castell JV, Raunio H, Gomez-Lechon MJ, and Pelkonen O (2000) CYP2A5/CYP2A6 expression in mouse and human hepatocytes treated with various in vivo inducers. Drug Metab Dispos 28:1321-1326.
124. Dresser GK, Spence JD, and Bailey DG (2000) Pharmacokinetic- pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition. Clin Pharmacokinet 38:41-57.
125. 3H]dopamine uptake into rat striatal slices by quaternary N-methylated nicotine metabolites. Life Sci 50:PL233-PL237.
126. Edwards RJ, Price RJ, Watts PS, Renwick AB, Tredger JM, Boobis AR, and Lake BG (2003) Induction of cytochrome P450 enzymes in cultured precision-cut human liver slices. Drug Metab Dispos 31:282-288.
127. Eldirdiri N, Ulgen M, Jacob P 3rd, and Gorrod JW (1997) The in vitro metabolism of norcotinine and related biotransformation products by microsomal preparations. Eur J Drug Metab Pharmacokinet 22:385-390.
128. English PB, Eskenazi B, and Christianson RE (1994) Black-white differences in serum cotinine levels among pregnant women and subsequent effects on infant birth weight. Am J Public Health 84:1439-1443.
129. Etzel RA, Greenberg RA, Haley NJ, and Loda FA (1985) Urine cotinine excretion in neonates exposed to tobacco smoke products in utero. J Pediatr 107:146-148.
130. Fant RV, Henningfield JE, Shiffman S, Strahs KR, and Reitberg DP (2000) A pharmacokinetic crossover study to compare the absorption characteristics of three transdermal nicotine patches. Pharmacol Biochem Behav 67:479-482.
131. Flammang AM, Gelboin HV, Aoyama T, Gonzalez FJ, and McCoy GD (1992) Nicotine metabolism by cDNA-expressed human cytochrome P-450s. Biochem Arch 8:1-8.
132. Fowler RT (1954) Redetermination of ionization constants of nicotine. J Appl Chem 4:449-452.
133. Fujita K and Kamataki T (2001) Screening of organosulfur compounds as inhibitors of human CYP2A6. Drug Metab Dispos 29:983-989.
134. Fukada A, Saito H, and Inui K (2002) Transport mechanisms of nicotine across the human intestinal epithelial cell line Caco-2. J Pharmacol Exp Ther 302:532-538.
135. Fukami T, Nakajima M, Yoshida R, Tsuchiya Y, Fujiki Y, Katoh M, McLeod HL, and Yokoi T (2004) A novel polymorphism of human CYP2A6 gene CYP2A6*17 has an amino acid substitution (V365M) that decreases enzymatic activity in vitro and in vivo. Clin Pharmacol Ther 76:519-527.
136. Gerbal-Chaloin S, Daujat M, Pascussi JM, Pichard-Garcia L, Vilarem MJ, and Maurel P (2002) Transcriptional regulation of CYP2C9 gene. Role of glucocorticoid receptor and constitutive androstane receptor. J Biol Chem 277:209-217.
137. Gerbal-Chaloin S, Pascussi JM, Pichard-Garcia L, Daujat M, Waechter F, Fabre JM, Carrere N, and Maurel P (2001) Induction of CYP2C genes in human hepatocytes in primary culture. Drug Metab Dispos 29:242-251.
138. Gervot L, Rochat B, Gautier JC, Bohnenstengel F, Kroemer H, de Berardinis V, Martin H, Beaune P, and de Waziers I (1999) Human CYP2B6: expression, inducibility and catalytic activities. Pharmacogenetics 9:295-306.
139. Getchell ML, Chen Y, Ding X, Sparks DL, and Getchell TV (1993) Immunohistochemical localization of a cytochrome P-450 isozyme in human nasal mucosa: age-related trends. Ann Otol Rhinol Laryngol 102:368-374.
140. Ghosheh O and Hawes EM (2002a) Microsomal N-glucuronidation of nicotine and cotinine: human hepatic interindividual, human intertissue and interspecies hepatic variation. Drug Metab Dispos 30:1478-1483.
141. Ghosheh O and Hawes EM (2002b) N-Glucuronidation of nicotine and cotinine in human: formation of cotinine glucuronide in liver microsomes and lack of catalysis by 10 examined UDP-glucuronosyltransferases. Drug Metab Dispos 30:991-996.
142. Gilmore J, Rotondo F, Pelletier AM, LaMarre J, Alaoui-Jamali M, and Kirby GM (2001) Identification of a 43-kDa protein in human liver cytosol that binds to the 3′-untranslated region of CYP2A6 mRNA. Biochem Pharmacol 62:669-678.
143. Giovino G, Sidney S, Gfroerer J, O'Malley P, Allen JA, Richter PA, and Cummings KM (2004) Epidemiology of menthol cigarette use. Nicotine Tob Res 6 (Suppl 1):S67-S81.
144. Godoy W, Albano RM, Moraes EG, Pinho PR, Nunes RA, Saito EH, Higa C, Filho IM, Kruel CD, Schirmer CC, et al. (2002) CYP2A6/2A7 and CYP2E1 expression in human oesophageal mucosa: regional and inter-individual variation in expression and relevance to nitrosamine metabolism. Carcinogenesis 23:611-616.
145. Gori GB, Benowitz NL, and Lynch CJ (1986) Mouth versus deep airways absorption of nicotine in cigarette smokers. Pharmacol Biochem Behav 25:1181-1184.
146. Gori GB and Lynch CJ (1985) Analytical cigarette yields as predictors of smoke bioavailability. Regul Toxicol Pharmacol 5:314-326.
147. Gorrod JW and Aislaitner G (1994) The metabolism of alicyclic amines to reactive iminium ion intermediates. Eur J Drug Metab Pharmacokinet 19:209-217.
148. Gorrod JW and Hibberd AR (1982) The metabolism of nicotine-delta 1′(5′)-iminium ion, in vivo and in vitro. Eur J Drug Metab Pharmacokinet 7:293-298.
149. Gorrod JW and Jenner P (1975) The metabolism of tobacco alkaloids, in Essays in Toxicology (Hayes WJJ ed) pp 35-78, Academic Press, Inc., New York.
150. Gourlay SG and Benowitz NL (1996) The benefits of stopping smoking and the role of nicotine replacement therapy in older patients. Drugs Aging 9:8-23.
151. Gourlay SG and Benowitz NL (1997) Arteriovenous differences in plasma concentration of nicotine and catecholamines and related cardiovascular effects after smoking, nicotine nasal spray and intravenous nicotine. Clin Pharmacol Ther 62:453-463.
152. Gow PJ, Ghabrial H, Smallwood RA, Morgan DJ, and Ching MS (2001) Neonatal hepatic drug elimination. Pharmacol Toxicol 88:3-15.
153. Gries JM, Benowitz N, and Verotta D (1996) Chronopharmacokinetics of nicotine. Clin Pharmacol Ther 60:385-395.
154. Grusz-Harday E (1967) Fatal nicotine poisoning. Arch Toxikol 23:35-41.
155. Guthrie SK, Zubieta JK, Ohl L, Ni L, Koeppe RA, Minoshima S, and Domino EF (1999) Arterial/venous plasma nicotine concentrations following nicotine nasal spray. Eur J Clin Pharmacol 55:639-643.
156. Hadidi H, Zahlsen K, Idle JR, and Cholerton S (1997) A single amino acid substitution (Leu160His) in cytochrome P450 CYP2A6 causes switching from 7-hydroxylation to 3-hydroxylation of coumarin. Food Chem Toxicol 35:903-907.
157. Hammond DK, Bjercke RJ, Langone JJ, and Strobel HW (1991) Metabolism of nicotine by rat liver cytochromes P-450. Assessment utilizing monoclonal antibodies to nicotine and cotinine. Drug Metab Dispos 19:804-808.
158. Harke HP, Schuller D, Frahm B, and Mauch A (1974) Demethylation of nicotine and cotinine in pigs. Res Commun Chem Pathol Pharmacol 9:595-599.
159. Hatsukami D, Lexau B, Nelson D, Pentel PR, Sofuoglu M, and Goldman A (1998a) Effects of cotinine on cigarette self-administration. Psychopharmacology (Berl) 138:184-189.
160. Hatsukami D, Pentel PR, Jensen J, Nelson D, Allen SS, Goldman A, and Rafael D (1998b) Cotinine: effects with and without nicotine. Psychopharmacology (Berl) 135:141-150.
161. Hatsukami DK, Grillo M, Pentel PR, Oncken C, and Bliss R (1997) Safety of cotinine in humans: physiologic, subjective and cognitive effects. Pharmacol Biochem Behav 57:643-650.
162. Hecht SS (1998) Biochemistry, biology and carcinogenicity of tobacco-specific N-nitrosamines. Chem Res Toxicol 11:559-603.
163. Hecht SS (2003) Tobacco carcinogens, their biomarkers and tobacco-induced cancer. Nat Rev Cancer 3:733-744.
164. Hecht SS, Carmella SG, Chen M, Dor Koch JF, Miller AT, Murphy SE, Jensen JA, Zimmerman CL, and Hatsukami DK (1999a) Quantitation of urinary metabolites of a tobacco-specific lung carcinogen after smoking cessation. Cancer Res 59:590-596.
165. Hecht SS, Carmella SG, and Murphy SE (1999b) Effects of watercress consumption on urinary metabolites of nicotine in smokers. Cancer Epidemiol Biomarkers Prev 8:907-913.
166. Hecht SS, Hatsukami DK, Bonilla LE, and Hochalter JB (1999c) Quantitation of 4-oxo-4-(3-pyridyl)butanoic acid and enantiomers of 4-hydroxy-4-(3-pyridyl) butanoic acid in human urine: a substantial pathway of nicotine metabolism. Chem Res Toxicol 12:172-179.
167. Hecht SS, Hochalter JB, Villalta PW, and Murphy SE (2000) 2′-Hydroxylation of nicotine by cytochrome P450 2A6 and human liver microsomes: formation of a lung carcinogen precursor. Proc Natl Acad Sci USA 97:12493-12497.
168. Hecht SS and Hoffmann D (1989) The relevance of tobacco-specific nitrosamines to human cancer. Cancer Surv 8:273-294.
169. Hellmold H, Rylander T, Magnusson M, Reihner E, Warner M, and Gustafsson JA (1998) Characterization of cytochrome P450 enzymes in human breast tissue from reduction mammaplasties. J Clin Endocrinol Metab 83:886-895.
170. Henningfield JE and Keenan RM (1993) Nicotine delivery kinetics and abuse liability. J Consult Clin Psychol 61:743-750.
171. Henningfield JE, Stapleton JM, Benowitz NL, Grayson RF, and London ED (1993) Higher levels of nicotine in arterial than in venous blood after cigarette smoking. Drug Alcohol Depend 33:23-29.
172. Herzig KE, Callaway E, Halliday R, Naylor H, and Benowitz NL (1998) Effects of cotinine on information processing in nonsmokers. Psychopharmacology (Berl) 135:127-132.
173. Hesse LM, He P, Krishnaswamy S, Hao Q, Hogan K, Moltke LL, Greenblatt DJ, and Court MH (2004) Pharmacogenetic determinants of interindividual variability in bupropion hydroxylation by cytochrome P450 2B6 in human liver microsomes. Pharmacogenetics 14:225-238.
174. Hibberd AR and Gorrod JW (1981) Nicotine delta 1 ″(5)′ iminium ion: a reactive intermediate in nicotine metabolism. Adv Exp Med Biol 136:1121-1131.
175. Hibberd AR and Gorrod JW (1985) Comparative N-oxidation of nicotine and cotinine by hepatic microsomes, in Biological Oxidation of Nitrogen in Organic Molecules (Gorrod JW and Damani LA eds) pp 246-250, Ellis Horwood Ltd, Chichester, UK.
176. Holladay MW, Dart MJ, and Lynch JK (1997) Neuronal nicotinic acetylcholine receptors as targets for drug discovery. J Med Chem 40:4169-4194.
177. Howard LA, Ahluwalia JS, Lin SK, Sellers EM, and Tyndale RF (2003a) CYP2E1*1D regulatory polymorphism: association with alcohol and nicotine dependence. Pharmacogenetics 13:321-328.
178. Howard LA, Miksys S, Hoffmann E, Mash D, and Tyndale RF (2003b) Brain CYP2E1 is induced by nicotine and ethanol in rat and is higher in smokers and alcoholics. Br J Pharmacol 138:1376-1386.
179. Hukkanen J, Gourlay SG, Kenkare S, and Benowitz NL (2005) Influence of menstrual cycle on CYP2A6 activity and cardiovascular effects of nicotine. Clin Pharmacol Ther, in press.
180. Hukkanen J, Pelkonen O, Hakkola J, and Raunio H (2002) Expression and regulation of xenobiotic-metabolizing cytochrome P450 (CYP) enzymes in human lung. Crit Rev Toxicol 32:391-411.
181. Hukkanen J, Vaisanen T, Lassila A, Piipari R, Anttila S, Pelkonen O, Raunio H, and Hakkola J (2003) Regulation of CYP3A5 by glucocorticoids and cigarette smoke in human lung-derived cells. J Pharmacol Exp Ther 304:745-752.
182. Hurt RD, Dale LC, Fredrickson PA, Caldwell CC, Lee GA, Offord KP, Lauger GG, Marusic Z, Neese LW, and Lundberg TG (1994) Nicotine patch therapy for smoking cessation combined with physician advice and nurse follow-up. One-year outcome and percentage of nicotine replacement. JAMA (J Am Med Assoc) 271:595-600.
183. Iscan M, Rostami H, Guray T, Pelkonen O, and Rautio A (1994) Interindividual variability of coumarin 7-hydroxylation in a Turkish population. Eur J Clin Pharmacol 47:315-318.
184. Iwase A, Aiba M, and Kira S (1991) Respiratory nicotine absorption in non-smoking females during passive smoking. Int Arch Occup Environ Health 63:139-143.
185. Jacob P 3rd and Benowitz NL (1991) Oxidative metabolism of nicotine in vivo, in Effects of Nicotine on Biological Systems (Adlkofer F and Thurau K eds) pp 35-44, Birkhauser Verlag, Basel.
186. Jacob P 3rd, Shulgin AT, and Benowitz NL (1990) Synthesis of (3′R,5′S)-trans-3′-hydroxycotinine, a major metabolite of nicotine. Metabolic formation of 3′-hydroxycotinine in humans is highly stereoselective. J Med Chem 33:1888-1891.
187. Jacob P 3rd, Ulgen M, and Gorrod JW (1997) Metabolism of (-)-(S)-nicotine by guinea pig and rat brain: identification of cotinine. Eur J Drug Metab Pharmacokinet 22:391-394.
188. Jacob P 3rd, Yu L, Shulgin AT, and Benowitz NL (1999) Minor tobacco alkaloids as biomarkers for tobacco use: comparison of users of cigarettes, smokeless tobacco, cigars and pipes. Am J Public Health 89:731-736.
189. Jain KK (2004) Modulators of nicotinic acetylcholine receptors as analgesics. Curr Opin Investig Drugs 5:76-81.
190. Jani N and Regueiro MD (2002) Medical therapy for ulcerative colitis. Gastroenterol Clin North Am 31:147-166.
191. Janmohamed A, Dolphin CT, Phillips IR, and Shephard EA (2001) Quantification and cellular localization of expression in human skin of genes encoding flavin-containing monooxygenases and cytochromes P450. Biochem Pharmacol 62:777-786.
192. Jarvis MJ, Boreham R, Primatesta P, Feyerabend C, and Bryant A (2001) Nicotine yield from machine-smoked cigarettes and nicotine intakes in smokers: evidence from a representative population survey. J Natl Cancer Inst 93:134-138.
193. Jenner P and Gorrod JW (1973) Comparative in vitro hepatic metabolism of some tertiary N-methyl tobacco alkaloids in various species. Res Commun Chem Pathol Pharmacol 6:829-843.
194. Jenner P, Gorrod JW, and Beckett AH (1973) Species variation in the metabolism of R-(+)- and S-(-)-nicotine by alpha-C- and N-oxidation in vitro. Xenobiotica 3:573-580.
195. Johansson CJ, Olsson P, Bende M, Carlsson T, and Gunnarsson PO (1991) Absolute bioavailability of nicotine applied to different nasal regions. Eur J Clin Pharmacol 41:585-588.
196. Kawamoto T, Kakizaki S, Yoshinari K, and Negishi M (2000) Estrogen activation of the nuclear orphan receptor CAR (constitutive active receptor) in induction of the mouse Cyp2b10 gene. Mol Endocrinol 14:1897-1905.
197. Keenan RM, Hatsukami DK, Pentel PR, Thompson TN, and Grillo MA (1994) Pharmacodynamic effects of cotinine in abstinent cigarette smokers. Clin Pharmacol Ther 55:581-590.
198. Kemp PM, Sneed GS, George CE, and Distefano RF (1997) Postmortem distribution of nicotine and cotinine from a case involving the simultaneous administration of multiple nicotine transdermal systems. J Anal Toxicol 21:310-313.
199. Khan IM, Stanislaus S, Zhang L, Taylor P, and Yaksh TL (2001) A-85380 and epibatidine each interact with disparate spinal nicotinic receptor subtypes to achieve analgesia and nociception. J Pharmacol Exp Ther 297:230-239.
200. Kharasch ED, Hankins DC, and Taraday JK (2000) Single-dose methoxsalen effects on human cytochrome P-450 2A6 activity. Drug Metab Dispos 28:28-33.
201. Kintz P, Henrich A, Cirimele V, and Ludes B (1998) Nicotine monitoring in sweat with a sweat patch. J Chromatogr B Biomed Sci Appl 705:357-361.
202. Kirby GM, Batist G, Alpert L, Lamoureux E, Cameron RG, and Alaoui-Jamali MA (1996) Overexpression of cytochrome P-450 isoforms involved in aflatoxin B1 bioactivation in human liver with cirrhosis and hepatitis. Toxicol Pathol 24:458-467.
203. Kitagawa H, Takenouchi T, Azuma R, Wesnes KA, Kramer WG, Clody DE, and Burnett AL (2003) Safety, pharmacokineties and effects on cognitive function of multiple doses of GTS-21 in healthy, male volunteers. Neuropsychopharmacology 28:542-551.
204. Kitagawa K, Kunugita N, Katoh T, Yang M, and Kawamoto T (1999) The significance of the homozygous CYP2A6 deletion on nicotine metabolism: a new genotyping method of CYP2A6 using a single PCR-RFLP. Biochem Biophys Res Commun 262:146-151.
205. Kitagawa K, Kunugita N, Kitagawa M, and Kawamoto T (2001) CYP2A6*6, a novel polymorphism in cytochrome p450 2A6, has a single amino acid substitution (R128Q) that inactivates enzymatic activity. J Biol Chem 276:17830-17835.
206. Kiyotani K, Fujieda M, Yamazaki H, Shimada T, Guengerich FP, Parkinson A, Nakagawa K, Ishizaki T, and Kamataki T (2002) Twenty one novel single nucleotide polymorphisms (SNPs) of the CYP2A6 gene in Japanese and Caucasians. Drug Metab Pharmacokin 17:482-487.
207. Kiyotani K, Yamazaki H, Fujieda M, Iwano S, Matsumura K, Satarug S, Ujjin P, Shimada T, Guengerich FP, Parkinson A, et al. (2003) Decreased coumarin 7-hydroxylase activities and CYP2A6 expression levels in humans caused by genetic polymorphism in CYP2A6 promoter region (CYP2A6*9). Pharmacogenetics 13:689-695.
208. Klus H and Kuhn H (1977) A study of the optical activity of smoke nicotines. Fachliche Mitt Oesterr Tabakregie 17:331-336.
209. Koenigs LL, Peter RM, Thompson SJ, Rettie AE, and Trager WF (1997) Mechanism-based inactivation of human liver cytochrome P450 2A6 by 8-methoxypsoralen. Drug Metab Dispos 25:1407-1415.
210. Koskela S, Hakkola J, Hukkanen J, Pelkonen O, Sorri M, Saranen A, Anttila S, Fernandez-Salguero P, Gonzalez F, and Raunio H (1999) Expression of CYP2A genes in human liver and extrahepatic tissues. Biochem Pharmacol 57:1407-1413.
211. Kozlowski LT, Mehta NY, Sweeney CT, Schwartz SS, Vogler GP, Jarvis MJ, and West RJ (1998) Filter ventilation and nicotine content of tobacco in cigarettes from Canada, the United Kingdom and the United States. Tob Control 7:369-375.
212. Kratz F (1976) Coumarin-7-hydroxylase activity in microsomes from needle biopsies of normal and diseased human liver. Eur J Clin Pharmacol 10:133-137.
213. Krause RJ, Lash LH, and Elfarra AA (2003) Human kidney flavin-containing monooxygenases and their potential roles in cysteine s-conjugate metabolism and nephrotoxicity. J Pharmacol Exp Ther 304:185-191.
214. Krul C and Hageman G (1998) Analysis of urinary caffeine metabolites to assess biotransformation enzyme activities by reversed-phase high-performance liquid chromatography. J Chromatogr B Biomed Sci Appl 709:27-34.
215. Kuehl GE and Murphy SE (2003a) N-Glucuronidation of nicotine and cotinine by human liver microsomes and heterologously expressed UDP- glucuronosyltransferases. Drug Metab Dispos 31:1361-1368.
216. Kuehl GE and Murphy SE (2003b) N-Glucuronidation of trans-3′- hydroxycotinine by human liver microsomes. Chem Res Toxicol 16:1502-1506.
217. Kwon JT, Nakajima M, Chai S, Yom YK, Kim HK, Yamazaki H, Sohn DR, Yamamoto T, Kuroiwa Y, and Yokoi T (2001) Nicotine metabolism and CYP2A6 allele frequencies in Koreans. Pharmacogenetics 11:317-323.
218. Kyerematen GA, Morgan M, Warner G, Martin LF, and Vesell ES (1990a) Metabolism of nicotine by hepatocytes. Biochem Pharmacol 40:1747-1756.
219. Kyerematen GA, Morgan ML, Chattopadhyay B, deBethizy JD, and Vesell ES (1990b) Disposition of nicotine and eight metabolites in smokers and nonsmokers: identification in smokers of two metabolites that are longer lived than cotinine. Clin Pharmacol Ther 48:641-651.
220. Lamba V, Lamba J, Yasuda K, Strom S, Davila J, Hancock ML, Packenthal JD, Rogan PK, Ring B, Wrighton SA, et al. (2003) Hepatic CYP2B6 expression: gender and ethnic differences and relationship to CYP2B6 genotype and CAR (constitutive androstane receptor) expression. J Pharmacol Exp Ther 307:906-922.
221. Langmann P, Bienert A, Zilly M, Vath T, Richter E, and Klinker H (2000) Influence of smoking on cotinine and caffeine plasma levels in patients with alcoholic liver cirrhosis. Eur J Med Res 5:217-221.
222. Lechevrel M, Casson AG, Wolf CR, Hardie LJ, Flinterman MB, Montesano R, and Wild CP (1999) Characterization of cytochrome P450 expression in human oesophageal mucosa. Carcinogenesis 20:243-248.
223. Lee BL, Benowitz NL, and Jacob P 3rd (1987) Influence of tobacco abstinence on the disposition kinetics and effects of nicotine. Clin Pharmacol Ther 41:474-479.
224. Lee BL, Jacob P 3rd, Jarvik ME, and Benowitz NL (1989) Food and nicotine metabolism. Pharmacol Biochem Behav 33:621-625.
225. Leete E (1983) Biosynthesis and metabolism of the tobacco alkaloids, in Alkaloids: Chemical and Biological Perspectives (Pelletier SW ed) pp 85-152, John Wiley & Sons, New York.
226. Le Gal A, Dreano Y, Lucas D, and Berthou F (2003) Diversity of selective environmental substrates for human cytochrome P450 2A6: alkoxyethers, nicotine, coumarin, N-nitrosodiethylamine and N-nitrosobenzylmethylamine. Toxicol Lett 144:77-91.
227. Leong JW, Dore ND, Shelley K, Holt EJ, Laing IA, Palmer LJ, and LeSouef PN (1998) The elimination half-life of urinary cotinine in children of tobacco-smoking mothers. Pulm Pharmacol Ther 11:287-290.
228. Li Y and Gorrod JW (1994) N-Hydroxymethylnorcotinine, a new primary in vitro metabolite of cotinine. Xenobiotica 24:409-415.
229. Lindell G, Farnebo LO, Chen D, Nexo E, Rask Madsen J, Bukhave K, and Graffner H (1993) Acute effects of smoking during modified sham feeding in duodenal ulcer patients. An analysis of nicotine, acid secretion, gastrin, catecholamines, epidermal growth factor, prostaglandin E2 and bile acids. Scand J Gastroenterol 28:487-494.
230. Lindell G, Lunell E, and Graffner H (1996) Transdermally administered nicotine accumulates in gastric juice. Eur J Clin Pharmacol 51:315-318.
231. Liston HL, Markowitz JS, and DeVane CL (2001) Drug glucuronidation in clinical psychopharmacology. J Clin Psychopharmacol 21:500-515.
232. Liu X, Castagnoli K, Van Der Schyf CJ, and Castagnoli N Jr (2000) Studies on the in vivo biotransformation of the tobacco alkaloid beta-nicotyrine. Chem Res Toxicol 13:336-341.
233. Liu X, Jacob P 3rd, and Castagnoli N Jr (1993) The metabolic fate of the minor tobacco alkaloids, in Nicotine and Related Alkaloids: Absorption, Distribution, Metabolism and Excretion (Gorrod JW and Wahren J eds) pp 129-145, Chapman & Hall, London.
234. Liu X, Zang L, Van der Schyf CJ, Igarashi K, Castagnoli K, and Castagnoli N Jr (1999) Studies on the pyrrolinone metabolites derived from the tobacco alkaloid 1-methyl-2-(3-pyridinyl)pyrrole (beta-nicotyrine). Chem Res Toxicol 12:508-512.
235. Lu GH and Ralapati S (1998) Application of high-performance capillary electrophoresis to the quantitative analysis of nicotine and profiling of other alkaloids in ATF-regulated tobacco products. Electrophoresis 19:19-26.
236. Luck W and Nau H (1984) Nicotine and cotinine concentrations in serum and milk of nursing smokers. Br J Clin Pharmacol 18:9-15.
237. Luck W, Nau H, Hansen R, and Steldinger R (1985) Extent of nicotine and cotinine transfer to the human fetus, placenta and amniotic fluid of smoking mothers. Dev Pharmacol Ther 8:384-395.
238. Lunell E, Bergstrom M, Antoni G, Langstrom B, and Nordberg A (1996) Nicotine deposition and body distribution from a nicotine inhaler and a cigarette studied with positron emission tomography. Clin Pharmacol Ther 59:593-594.
239. Lunell E, Molander L, Ekberg K, and Wahren J (2000) Site of nicotine absorption from a vapour inhaler-comparison with cigarette smoking. Eur J Clin Pharmacol 55:737-741.
240. MacDougall JM, Fandrick K, Zhang X, Serafin SV, and Cashman JR (2003) Inhibition of human liver microsomal (5)-nicotine oxidation by (-)-menthol and analogues. Chem Res Toxicol 16:988-993.
241. Mackay J and Eriksen M (2002) The Tobacco Atlas, World Health Organization, Geneva.
242. Madan A, Graham HA, Carroll KM, Mudra DR, Burton LA, Krueger LA, Downey AD, Czervrinski M, Forster J, Ribadeneira MD, et al. (2003) Effects of prototypical microsomal enzyme inducers on cytochrome P450 expression in cultured human hepatocytes. Drug Metab Dispos 31:421-431.
243. Maenpaa J, Juvonen R, Raunio H, Rautio A, and Pelkonen O (1994) Metabolic interactions of methoxsalen and coumarin in humans and mice. Biochem Pharmacol 48:1363-1369.
244. Maglich JM, Parks DJ, Moore LB, Collins JL, Goodwin B, Billin AN, Stoltz CA, Kliewer SA, Lambert MH, Willson TM, et al. (2003) Identification of a novel human constitutive androstane receptor (CAR) agonist and its use in the identification of CAR target genes. J Biol Chem 278:17277-17283.
245. Mattes WB and Li AP (1997) Quantitative reverse transcriptase/PCR assay for the measurement of induction in cultured hepatocytes. Chem Biol Interact 107:47-61.
246. Maurice M, Emiliani S, Dalet-Beluche I, Derancourt J, and Lange R (1991) Isolation and characterization of a cytochrome P450 of the IIA subfamily from human liver microsomes. Eur J Biochem 200:511-517.
247. McBride JS, Altman DG, Klein M, and White W (1998) Green tobacco sickness. Tob Control 7:294-298.
248. McCarver DG, Byun R, Hines RN, Hichme M, and Wegenek W (1998) A genetic polymorphism in the regulatory sequences of human CYP2E1: association with increased chlorzoxazone hydroxylation in the presence of obesity and ethanol intake. Toxicol Appl Pharmacol 152:276-281.
249. McCracken NW, Cholerton S, and Idle JR (1992) Cotinine formation by cDNA-expressed human cytochromes P450. Med Sci Res 20:877-878.
250. McCusker K, McNabb E, and Bone R (1982) Plasma nicotine levels in pipe smokers. JAMA (J Am Med Assoc) 248:577-878.
251. McGurk KA, Brierley CH, and Burchell B (1998) Drug glucuronidation by human renal UDP-glucuronosyltransferases. Biochem Pharmacol 55:1005-1012.
252. McKennis H Jr, Schwartz SL, and Bowman ER (1964) Alternate routes in the metabolic degradation of the pyrrolidine ring of nicotine. J Biol Chem 239:3990-3996.
253. McKennis H Jr, Turnbull LB, and Bowman ER (1963a) N-Methylation of nicotine and cotinine in vivo. J Biol Chem 238:719-723.
254. McKennis H Jr, Turnbull LB, Bowman ER, and Schwartz SL (1962) The corrected structure of a ketoamide arising from the metabolism of (-)-nicotine. J Am Chem Soc 84:4598-4599.
255. McKennis H Jr, Turnbull LB, Bowman ER, and Tamaki E (1963b) The synthesis of hydroxycotinine and studies on its structure. J Org Chem 28:383-387.
256. McNabb ME (1984) Chewing nicotine gum for 3 months: what happens to plasma nicotine levels? Can Med Assoc J 131:589-592.
257. McNabb ME, Ebert RV, and McCusker K (1982) Plasma nicotine levels produced by chewing nicotine gum. JAMA (J Am Med Assoc) 248:865-868.
258. Meger M, Meger-Kossien I, Schuler-Metz A, Janket D, and Scherer G (2002) Simultaneous determination of nicotine and eight nicotine metabolites in urine of smokers using liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 778:251-261.
259. Mellick LB, Makowski T, Mellick GA, and Borger R (1999) Neuromuscular blockade after ingestion of tree tobacco (Nicotiana glauca). Ann Emerg Med 34:101-104.
260. Menzaghi F, Whelan KT, Risbrough VB, Rao TS, and Lloyd GK (1997) Effects of a novel cholinergic ion channel agonist SIB-1765F on locomotor activity in rats. J Pharmacol Exp Ther 280:384-392.
261. Merkel U, Sigusch H, and Hoffmann A (1994) Grapefruit juice inhibits 7-hydroxylation of coumarin in healthy volunteers. Eur J Clin Pharmacol 46:175-177.
262. Messina ES, Tyndale RF, and Sellers EM (1997) A major role for CYP2A6 in nicotine C-oxidation by human liver microsomes. J Pharmacol Exp Ther 282:1608-1614.
263. Meunier V, Bourrie M, Julian B, Marti E, Guillou F, Berger Y, and Fabre G (2000) Expression and induction of CYP1A1/1A2, CYP2A6 and CYP3A4 in primary cultures of human hepatocytes: a 10-year follow-up. Xenobiotica 30:589-607.
264. Miksys S, Lerman C, Shields PG, Mash DC, and Tyndale RF (2003) Smoking, alcoholism and genetic polymorphisms alter CYP2B6 levels in human brain. Neuropharmacology 45:122-132.
265. Miksys S, Rao Y, Hoffmann E, Mash DC, and Tyndale RF (2002) Regional and cellular expression of CYP2D6 in human brain: higher levels in alcoholics. J Neurochem 82:1376-1387.
266. Mizrachi N, Levy S, and Goren ZQ (2000) Fatal poisoning from Nicotiana glauca leaves: identification of anabasine by gas-chromatography/mass spectrometry. J Forensic Sci 45:736-741.
267. Molander L, Hansson A, and Lunell E (2001) Pharmacokinetics of nicotine in healthy elderly people. Clin Pharmacol Ther 69:57-65.
268. Molander L, Hansson A, Lunell E, Alainentalo L, Hoffmann M, and Larsson R (2000) Pharmacokinetics of nicotine in kidney failure. Clin Pharmacol Ther 68:250-260.
269. Molander L and Lunell E (2001) Pharmacokinetic investigation of a nicotine sublingual tablet. Eur J Clin Pharmacol 56:813-819.
270. Molander L, Lunell E, Andersson SB, and Kuylenstierna F (1996) Dose released and absolute bioavailability of nicotine from a nicotine vapor inhaler. Clin Pharmacol Ther 59:394-400.
271. Moore LB, Parks DJ, Jones SA, Bledsoe RK, Consler TG, Stimmel JB, Goodwin B, Liddle C, Blanchard SG, Willson TM, et al. (2000) Orphan nuclear receptors constitutive androstane receptor and pregnane X receptor share xenobiotic and steroid ligands. J Biol Chem 275:15122-15127.
272. Moriwaki Y, Yamamoto T, Takahashi S, Tsutsumi Z, and Hada T (2001) Widespread cellular distribution of aldehyde oxidase in human tissues found by immunohistochemistry staining. Histol Histopathol 16:745-753.
273. Munzel PA, Schmohl S, Heel H, Kalberer K, Bock-Hennig BS, and Bock KW (1999) Induction of human UDP glucuronosyltransferases (UGT1A6, UGT1A9 and UGT2B7) by t-butylhydroquinone and 2,3,7,8-tetrachlorodibenzo-p-dioxin in Caco-2 cells. Drug Metab Dispos 27:569-573.
274. Muranaka H, Higashi E, Itani S, and Shimizu Y (1988) Evaluation of nicotine, cotinine, thiocyanate, carboxyhemoglobin and expired carbon monoxide as biochemical tobacco smoke uptake parameters. Int Arch Occup Environ Health 60:37-41.
275. Murphy PJ (1973) Enzymatic oxidation of nicotine to nicotine 1′(5′) iminium ion. A newly discovered intermediate in the metabolism of nicotine. J Biol Chem 248:2796-2800.
276. Murphy SE, Johnson LM, Losey LM, Carmella SG, and Hecht SS (2001) Consumption of watercress fails to alter coumarin metabolism in humans. Drug Metab Dispos 29:786-788.
277. Murphy SE, Johnson LM, and Pullo DA (1999) Characterization of multiple products of cytochrome P450 2A6-catalyzed cotinine metabolism. Chem Res Toxicol 12:639-645.
278. Nakajima M, Kuroiwa Y, and Yokoi T (2002a) Interindividual differences in nicotine metabolism and genetic polymorphisms of human CYP2A6. Drug Metab Rev 34:865-877.
279. Nakajima M, Kwon JT, Tanaka N, Zenta T, Yamamoto Y, Yamamoto H, Yamazaki H, Yamamoto T, Kuroiwa Y, and Yokoi T (2001) Relationship between interindividual differences in nicotine metabolism and CYP2A6 genetic polymorphism in humans. Clin Pharmacol Ther 69:72-78.
280. Nakajima M, Tanaka E, Kwon JT, and Yokoi T (2002b) Characterization of nicotine and cotinine N-glucuronidations in human liver microsomes. Drug Metab Dispos 30:1484-1490.
281. Nakajima M, Yamagishi S, Yamamoto H, Yamamoto T, Kuroiwa Y, and Yokoi T (2000) Deficient cotinine formation from nicotine is attributed to the whole deletion of the CYP2A6 gene in humans. Clin Pharmacol Ther 67:57-69.
282. Nakajima M, Yamamoto T, Nunoya K, Yokoi T, Nagashima K, Inoue K, Funae Y, Shimada N, Kamataki T, and Kuroiwa Y (1996a) Characterization of CYP2A6 involved in 3′-hydroxylation of cotinine in human liver microsomes. J Pharmacol Exp Ther 277:1010-1015.
283. Nakajima M, Yamamoto T, Nunoya K, Yokoi T, Nagashima K, Inoue K, Funae Y, Shimada N, Kamataki T, and Kuroiwa Y (1996b) Role of human cytochrome P4502A6 in C-oxidation of nicotine. Drug Metab Dispos 24:1212-1217.
284. Nakayama H, Okuda H, Nakashima T, Imaoka S, and Funae Y (1993) Nicotine metabolism by rat hepatic cytochrome P450s. Biochem Pharmacol 45:2554-2556.
285. Nasirov SK, Ryabchenko VP, Khalikova FR, Khazbievich IS, and Kashkova EK (1978) Anabasine hydrochloride - a new antismoking agent. Khim-Farm Zh 12:149-152.
286. Neurath GB (1994) Aspects of the oxidative metabolism of nicotine. Clin Investig 72:190-195.
287. Neurath GB, Dunger M, Krenz O, Orth D, and Pein FG (1988) Trans-3′-hydroxycotinine - a main metabolite in smokers. Klin Wochenschr 66 (Suppl 11):2-4.
288. Neurath GB, Dunger M, Orth D, and Pein FG (1987) Trans-3′- hydroxycotinine as a main metabolite in urine of smokers. Int Arch Occup Environ Health 59:199-201.
289. Neurath GB, Orth D, and Pein FG (1991) Detection of nornicotine in human urine after infusion of nicotine, in Effects of Nicotine on Biological Systems (Adlkofer F and Thurau K eds) pp 45-49, Birkhauser Verlag, Basel.
290. Nguyen T, Sherratt PJ, and Pickett CB (2003) Regulatory mechanisms controlling gene expression mediated by the antioxidant response element. Annu Rev Pharmacol Toxicol 43:233-260.
291. Nguyen TL (1976) Alpha-Carbon Hydroxylation in the Metabolism of Tobacco Alkaloids. Ph.D. thesis, University of California, San Francisco, CA.
292. Nguyen TL, Gruenke LD, and Castagnoli N Jr (1979) Metabolic oxidation of nicotine to chemically reactive intermediates. J Med Chem 22:259-263.
293. Niemela O, Parkkila S, Juvonen RO, Viitala K, Gelboin HV, and Pasanen M (2000) Cytochromes P450 2A6, 2E1 and 3A and production of protein-aldehyde adducts in the liver of patients with alcoholic and non-alcoholic liver diseases. J Hepatol 33:893-901.
294. Nolin TD, Frye RF, and Matzke GR (2003) Hepatic drug metabolism and transport in patients with kidney disease. Am J Kidney Dis 42:906-925.
295. Nowell S, Sweeney C, Hammons G, Kadlubar FF, and Lang NP (2002) CYP2A6 activity determined by caffeine phenotyping: association with colorectal cancer risk. Cancer Epidemiol Biomarkers Prev 11:377-383.
296. Nuesslein TG, Beckers D, and Rieger CH (1999) Cotinine in meconium indicates risk for early respiratory tract infections. Hum Exp Toxicol 18:283-290.
297. Nunoya K, Yokoi T, Kimura K, Inoue K, Kodama T, Funayama M, Nagashima K, Funae Y, Green C, Kinoshita M, et al. (1998) A new deleted allele in the human cytochrome P450 2A6 (CYP2A6) gene found in individuals showing poor metabolic capacity to coumarin and (+)-cis-3,5-dimethyl-2-(3-pyridyl)tniazolidin-4-one hydrochloride (SM-12502). Pharmacogenetics 8:239-249.
298. Nunoya K, Yokoi T, Takahashi Y, Kimura K, Kinoshita M, and Kamataki T (1999a) Homologous unequal cross-over within the human CYP2A gene cluster as a mechanism for the deletion of the entire CYP2A6 gene associated with the poor metabolizer phenotype. J Biochem (Tokyo) 126:402-407.
299. Nunoya KI, Yokoi T, Kimura K, Kainuma T, Satoh K, Kinoshita M, and Kamataki T (1999b) A new CYP2A6 gene deletion responsible for the in vivo polymorphic metabolism of (+)-cis-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one hydrochloride in humans. J Pharmacol Exp Ther 289:437-442.
300. Nwosu CG and Crooks PA (1988) Species variation and stereoselectivity in the metabolism of nicotine enantiomers. Xenobiotica 18:1361-1372.
301. Obach RS (2004) Potent inhibition of human liver aldehyde oxidase by raloxifene. Drug Metab Dispos 32:89-97.
302. Obach RS and van Vunakis H (1990) Radioimmunoassay of nicotine-delta 1′(5′)-iminium ion, an intermediate formed during the metabolism of nicotine to cotinine. Drug Metab Dispos 18:508-513.
303. Oscarson M (2001) Genetic polymorphisms in the cytochrome P450 2A6 (CYP2A6) gene: implications for interindividual differences in nicotine metabolism. Drug Metab Dispos 29:91-95.
304. Oscarson M, McLellan RA, Asp V, Ledesma M, Ruiz ML, Sinues B, Rautio A, and Ingelman-Sundberg M (2002) Characterization of a novel CYP2A7/CYP2A6 hybrid allele (CYP2A6*12) that causes reduced CYP2A6 activity. Hum Mutat 20:275-283.
305. Oscarson M, McLellan RA, Gullsten H, Agundez JA, Benitez J, Rautio A, Raunio H, Pelkonen O, and Ingelman-Sundberg M (1999a) Identification and characterisation of novel polymorphisms in the CYP2A locus: implications for nicotine metabolism. FEBS Lett 460:321-327.
306. Oscarson M, McLellan RA, Gullsten H, Yue QY, Lang MA, Bernai ML, Sinues B, Hirvonen A, Raunio H, Pelkonen O, et al. (1999b) Characterisation and PCR-based detection of a CYP2A6 gene deletion found at a high frequency in a Chinese population. FEBS Lett 448:105-110.
307. Ostrea EM Jr, Knapp DK, Romero A, Montes M, and Ostrea AR (1994) Meconium analysis to assess fetal exposure to nicotine by active and passive maternal smoking. J Pediatr 124:471-476.
308. Palmer CN, Coates PJ, Davies SE, Shephard EA, and Phillips IR (1992) Localization of cytochrome P-450 gene expression in normal and diseased human liver by in situ hybridization of wax-embedded archival material. Hepatology 16:682-687.
309. Pankow JF (2001) A consideration of the role of gas/particle partitioning in the deposition of nicotine and other tobacco smoke compounds in the respiratory tract. Chem Res Toxicol 14:1465-1481.
310. Pankow JF, Tavakoli AD, Luo W, and Isabelle LM (2003) Percent free base nicotine in the tobacco smoke particulate matter of selected commercial and reference cigarettes. Chem Res Toxicol 16:1014-1018.
311. Papadopoulos NM (1964) Formation of nornicotine and other metabolites from nicotine in vitro and in vivo. Can J Biochem Physiol 42:435-442.
312. Park SB, Jacob P 3rd, Benowitz NL, and Cashman JK (1993) Stereoselective metabolism of (S)-(-)-nicotine in humans: formation of trans-(S)-(-)-nicotine N-1′-oxide. Chem Res Toxicol 6:880-888.
313. Pasanen M, Rannala Z, Tooming A, Sotaniemi EA, Pelkonen O, and Rautio A (1997) Hepatitis A impairs the function of human hepatic CYP2A6 in vivo. Toxicology 123:177-184.
314. Paschke T, Riefler M, Schuler-Metz A, Wolz L, Scherer G, McBride CM, and Bepler G (2001) Comparison of cytochrome P450 2A6 polymorphism frequencies in Caucasians and African-Americans using a new one-step PCR-RFLP genotyping method. Toxicology 168:259-268.
315. Pascussi JM, Drocourt L, Gerbal-Chaloin S, Fabre JM, Maurel P, and Vilarem MJ (2001) Dual effect of dexamethasone on CYP3A4 gene expression in human hepatocytes. Sequential role of glucocorticoid receptor and pregnane X receptor. Eur J Biochem 268:6346-6358.
316. Pascussi JM, Gerbal-Chaloin S, Fabre JM, Maurel P, and Vilarem MJ (2000a) Dexamethasone enhances constitutive androstane receptor expression in human hepatocytes: consequences on cytochrome P450 gene regulation. Mol Pharmacol 58:1441-1450.
317. Pascussi JM, Gerbal-Chaloin S, Pichard-Garcia L, Daujat M, Fabre JM, Maurel P, and Vilarem MJ (2000b) Interleukin-6 negatively regulates the expression of pregnane X receptor and constitutively activated receptor in primary human hepatocytes. Biochem Biophys Res Commun 274:707-713.
318. Pastrakuljic A, Schwartz R, Simone C, Derewlany LO, Knie B, and Koren G (1998) Transplacental transfer and biotransformation studies of nicotine in the human placental cotyledon perfused in vitro. Life Sci 63:2333-2342.
319. Patterson F, Benowitz N, Shields P, Kaufmann V, Jepson C, Wileyto P, Kucharski S, and Lerman C (2003) Individual differences in nicotine intake per cigarette. Cancer Epidemiol Biomarkers Prev 12:468-471.
320. Pearce R, Greenway D, and Parkinson A (1992) Species differences and interindividual variation in liver microsomal cytochrome P450 2A enzymes: effects on coumarin, dicumarol and testosterone oxidation. Arch Biochem Biophys 298:211-225.
321. Pelkonen O, Rautio A, Raunio H, and Pasanen M (2000) CYP2A6: a human coumarin 7-hydroxylase. Toxicology 144:139-147.
322. Pelkonen O, Sotaniemi EA, and Ahokas JT (1985) Coumarin 7-hydroxylase activity in human liver microsomes. Properties of the enzyme and interspecies comparisons. Br J Clin Pharmacol 19:59-66.
323. Perez-Stable EJ, Herrera B, Jacob P 3rd, and Benowitz NL (1998) Nicotine metabolism and intake in black and white smokers. JAMA (J Am Med Assoc) 280:152-156.
324. Perry DC, Davila-Garcia MI, Stockmeier CA, and Kellar KJ (1999) Increased nicotinic receptors in brains from smokers: membrane binding and autoradiography studies. J Pharmacol Exp Ther 289:1545-1552.
325. Perry RJ, Griffiths W, Dextraze P, Solomon RJ, and Trebbin WM (1984) Elevated nicotine levels in patients undergoing hemodialysis. A role in cardiovascular mortality and morbidity? Am J Med 76:241-246.
326. Peterson LA, Trevor A, and Castagnoli N Jr (1987) Stereochemical studies on the cytochrome P-450 catalyzed oxidation of (S)-nicotine to the (S)-nicotine delta 1′(5′)-iminium species. J Med Chem 30:249-254.
327. Peto R, Lopez AD, Boreham J, Thun M, and Heath C Jr (1992) Mortality from tobacco in developed countries: indirect estimation from national vital statistics. Lancet 339:1268-1278.
328. Pitarque M, von Richter O, Oke B, Berkkan H, Oscarson M, and Ingelman-Sundberg M (2001) Identification of a single nucleotide polymorphism in the TATA box of the CYP2A6 gene: impairment of its promoter activity. Biochem Biophys Res Commun 284:455-460.
329. Pitarque M, von Richter O, Rodriguez-Antona C, Wang J, Oscarson M, and Ingelman-Sundberg M (2004) A nicotine C-oxidase gene (CYP2A6) polymorphism important for promoter activity. Hum Mutat 23:258-266.
330. Poland RE, Pechnick RN, Cloak CC, Wan YJ, Nuccio I, and Lin KM (2000) Effect of cigarette smoking on coumarin metabolism in humans. Nicotine Tob Res 2:351-354.
331. Pool WF, Godin CS, and Crooks PA (1985) Nicotine racemization during nicotine smoking. The Toxicologist 5:232.
332. Poole A and Urwin C (1976) The metabolism of (14C)nicotine by isolated rhesus monkey hepatocytes in vitro. Biochem Pharmacol 25:281-283.
333. Porchet HC, Benowitz NL, Sheiner LB, and Copeland JR (1987) Apparent tolerance to the acute effect of nicotine results in part from distribution kinetics. J Clin Investig 80:1466-1471.
334. Prather RD, Tu TG, Rolf CN, and Gorsline J (1993) Nicotine pharmacokinetics of Nicoderm (nicotine transdermal system) in women and obese men compared with normal-sized men. J Clin Pharmacol 33:644-649.
335. Quik M and Kulak JM (2002) Nicotine and nicotinic receptors; relevance to Parkinson's disease. Neurotoxicology 23:581-594.
336. Rae JM, Johnson MD, Lippman ME, and Flockhart DA (2001) Rifampin is a selective, pleiotropic inducer of drug metabolism genes in human hepatocytes: studies with cDNA and oligonucleotide expression arrays. J Pharmacol Exp Ther 299:849-857.
337. Rahnasto M, Raunio H, Poso A, and Juvonen RO (2003) More potent inhibition of human CYP2A6 than mouse CYP2A5 enzyme activities by derivatives of phenylethylamine and benzaldehyde. Xenobiotica 33:529-539.
338. Rao Y, Hoffmann E, Zia M, Bodin L, Zeman M, Sellers EM, and Tyndale RF (2000) Duplications and defects in the CYP2A6 gene: identification, genotyping and in vivo effects on smoking. Mol Pharmacol 58:747-755.
339. Rauma AL, Rautio A, Pasanen M, Pelkonen O, Torronen R, and Mykkanen H (1996) Coumarin 7-hydroxylation in long-term adherents of a strict uncooked vegan diet. Eur J Clin Pharmacol 50:133-137.
340. Raunio H, Juvonen R, Pasanen M, Pelkonen O, Paakko P, and Soini Y (1998) Cytochrome P4502A6 (CYP2A6) expression in human hepatocellular carcinoma. Hepatology 27:427-432.
341. Raunio H, Rautio A, Gullsten H, and Pelkonen O (2001) Polymorphisms of CYP2A6 and its practical consequences. Br J Clin Pharmacol 52:357-363.
342. Rautio A, Kraul H, Kojo A, Salmela E, and Pelkonen O (1992) Interindividual variability of coumarin 7-hydroxylation in healthy volunteers. Pharmacogenetics 2:227-233.
343. Rautio A, Salmela E, Arvela P, Pelkonen O, and Sotaniemi EA (1994) Assessment of CYP2A6 and CYP3A4 activities in vivo in different diseases in man, in Cytochrome P450: Biochemistry, Biophysics and Molecular Biology (Lechner MC ed) pp 519-521, John Libbey Eurotext, Paris.
344. Rebagliato M, Bolumar F, Florey Cdu V, Jarvis MJ, Perez-Hoyos S, Hernandez-Aguado I, and Avino MJ (1998) Variations in cotinine levels in smokers during and after pregnancy. Am J Obstet Gynecol 178:568-571.
345. Ren Q, Murphy SE, Zheng Z, and Lazarus P (2000) O-Glucuronidation of the lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) by human UDP-glucuronosyltransferases 2B7 and 1A9. Drug Metab Dispos 28:1352-1360.
346. Robertson P, DeCory HH, Madan A, and Parkinson A (2000) In vitro inhibition and induction of human hepatic cytochrome P450 enzymes by modafinil. Drug Metab Dispos 28:664-671.
347. Rodrigues AD, Ferrero JL, Amann MT, Rotert GA, Cepa SP, Surber BW, Machinist JM, Tich NR, Sullivan JP, Garvey DS, et al. (1994) The in vitro hepatic metabolism of ABT-418, a cholinergic channel activator, in rats, dogs, cynomolgus monkeys and humans. Drug Metab Dispos 22:788-798.
348. Rodrigues AD, Kukulka MJ, Ferrero JL, and Cashman JR (1995) In vitro hepatic metabolism of ABT-418 in chimpanzee (Pan troglodytes). A unique pattern of microsomal flavin-containing monooxygenase-dependent stereoselective N′-oxidation. Drug Metab Dispos 23:1143-1152.
349. Rose JE, Behm FM, Westman EC, and Coleman RE (1999) Arterial nicotine kinetics during cigarette smoking and intravenous nicotine administration: implications for addiction. Drug Alcohol Depend 56:99-107.
350. Runkel M, Bourian M, Tegtmeier M, and Legrum W (1997) The character of inhibition of the metabolism of 1,2-benzopyrone (coumarin) by grapefruit juice in human. Eur J Clin Pharmacol 53:265-269.
351. Russell MA and Feyerabend C (1978) Cigarette smoking: a dependence on high-nicotine boli. Drug Metab Rev 8:29-57.
352. Russell MA, Jarvis M, Iyer R, and Feyerabend C (1980) Relation of nicotine yield of cigarettes to blood nicotine concentrations in smokers. Br Med J 280:972-976.
353. Saarikoski ST, Sata F, Husgafvel-Pursiainen K, Rautalahti M, Haukka J, Impivaara O, Jarvisalo J, Vainio H, and Hirvonen A (2000) CYP2D6 ultrarapid metabolizer genotype as a potential modifier of smoking behaviour. Pharmacogenetics 10:5-10.
354. Sabbagh MN, Lukas RJ, Sparks DL, and Reid RT (2002) The nicotinic acetylcholine receptor, smoking and Alzheimer's disease. J Alzheimers Dis 4:317-325.
355. Saitoh F, Noma M, and Kawashima N (1985) The alkaloid contents of sixty nicotiana species. Phytochemistry 24:477-480.
356. Satarug S, Lang MA, Yongvanit P, Sithithaworn P, Mairiang E, Mairiang P, Pelkonen P, Bartsch H, and Haswell-Elkins MR (1996) Induction of cytochrome P450 2A6 expression in humans by the carcinogenic parasite infection, opisthorchiasis viverrini. Cancer Epidemiol Biomarkers Prev 5:795-800.
357. Satarug S, Nishijo M, Ujjin P, Vanavanitkun Y, Baker JR, and Moore MR (2004) Effects of chronic exposure to low-level cadmium on renal tubular function and CYP2A6-mediated coumarin metabolism in healthy human subjects. Toxicol Lett 148:187-197.
358. Scheline RR (1978) Mammalian Metabolism of Plant Xenobiotics, Academic Press, London.
359. Schepers G, Demetriou D, Stabbert R, Diehl B, and Seeman JI (1999) 5′-Hydroxycotinine-N-oxide, a new nicotine metabolite isolated from rat urine. Xenobiotica 29:793-801.
360. Schepers G, Rustemeier K, Walk RA, and Hackenberg U (1993) Metabolism of S-nicotine in noninduced and aroclor-induced rats. Eur J Drug Metab Pharmacokinet 18:187-197.
361. Scherer G, Jarczyk L, Heller WD, Biber A, Neurath GB, and Adlkofer F (1988) Pharmacokinetics of nicotine, cotinine and 3′-hydroxycotinine in cigarette smokers. Klin Wochenschr 66 (Suppl 11):5-11.
362. Schievelbein H (1982) Nicotine, resorption and fate. Pharmacol Ther 18:233-248.
363. Schmeltz I and Hoffmann D (1977) Nitrogen containing compounds in tobacco and tobacco smoke. Chem Rev 77:295-311.
364. Schmidt R, Baumann F, Hanschmann H, Geissler F, and Preiss R (2001) Gender difference in ifosfamide metabolism by human liver microsomes. Eur J Drug Metab Pharmacokinet 26:193-200.
365. Schneider NG, Olmstead R, Mody FV, Doan K, Franzon M, Jarvik ME, and Steinberg C (1995) Efficacy of a nicotine nasal spray in smoking cessation: a placebo-controlled, double-blind trial. Addiction 90:1671-1682.
366. Schneider NG, Olmstead R, Nilsson F, Mody FV, Franzon M, and Doan K (1996) Efficacy of a nicotine inhaler in smoking cessation: a double-blind, placebo-controlled trial. Addiction 91:1293-1306.
367. Schneider NG, Olmstead RE, Franzon MA, and Lunell E (2001) The nicotine inhaler: clinical pharmacokinetics and comparison with other nicotine treatments. Clin Pharmacokinet 40:661-684.
368. Schoedel KA, Hoffmann EB, Rao Y, Sellers EM, and Tyndale RF (2004) Ethnic variation in CYP2A6 and association of genetically slow nicotine metabolism and smoking in adult Caucasians. Pharmacogenetics 14:615-626.
369. Schoedel KA, Sellers EM, Palmour R, and Tyndale RF (2003) Down-regulation of hepatic nicotine metabolism and a CYP2A6-like enzyme in African green monkeys after long-term nicotine administration. Mol Pharmacol 63:96-104.
370. Seaton M, Kyerematen GA, Morgan M, Jeszenka EV, and Vesell ES (1991) Nicotine metabolism in stumptailed macaques, Macaca arctoides. Drug Metab Dispos 19:946-954.
371. Seaton MJ and Vesell ES (1993) Variables affecting nicotine metabolism. Pharmacol Ther 60:461-500.
372. Seaton MJ, Vesell ES, Luo H, and Hawes EM (1993) Identification of radiolabeled metabolites of nicotine in rat bile. Synthesis of S-(-)-nicotine N-glucuronide and direct separation of nicotine-derived conjugates using high-performance liquid chromatography. J Chromatogr 621:49-53.
373. Selby P, Hackman R, Kapur B, Klein J, and Koren G (2001) Heavily smoking women who cannot quit in pregnancy: evidence of pharmacokinetic predisposition. Ther Drug Monit 23:189-191.
374. Sellers EM, Kaplan HL, and Tyndale RF (2000) Inhibition of cytochrome P450 2A6 increases nicotine's oral bioavailability and decreases smoking. Clin Pharmacol Ther 68:35-43.
375. Sellers EM, Ramamoorthy Y, Zeman MV, Djordjevic MV, and Tyndale RF (2003a) The effect of methoxsalen on nicotine and 4-(methylnitrosamino)-1-(3- pyridyl)-1-butanone (NNK) metabolism in vivo. Nicotine Tob Res 3:891-899.
376. Sellers EM, Tyndale RF, and Fernandes LC (2003b) Decreasing smoking behaviour and risk through CYP2A6 inhibition. Drug Discov Today 8:487-493.
377. Sensabaugh AJ and Cundiff RH (1967) A new technique for determining the pH of whole tobacco smoke. Tobacco Sci 164:28-33.
378. Shigenaga MK, Kim BH, Caldera-Munoz P, Cairns T, Jacob P 3rd, Trevor AJ, and Castagnoli N Jr (1989) Liver and lung microsomal metabolism of the tobacco alkaloid beta-nicotyrine. Chem Res Toxicol 2:282-287.
379. 3H]nicotine to liver and lung microsomal macromolecules. Drug Metab Dispos 16:397-402.
380. Shimada T, Yamazaki H, and Guengerich FP (1996) Ethnic-related differences in coumarin 7-hydroxylation activities catalyzed by cytochrome P4502A6 in liver microsomes of Japanese and Caucasian populations. Xenobiotica 26:395-403.
381. Shimada T, Yamazaki H, Mimura M, Inui Y, and Guengerich FP (1994) Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians. J Pharmacol Exp Ther 270:414-423.
382. Shulgin AT, Jacob P 3rd, Benowitz NL, and Lau D (1987) Identification and quantitative analysis of cotinine-N-oxide in human urine. J Chromatogr 423:365-372.
383. Siegle I, Fritz P, Eckhardt K, Zanger UM, and Eichelbaum M (2001) Cellular localization and regional distribution of CYP2D6 mRNA and protein expression in human brain. Pharmacogenetics 11:237-245.
384. Siegmund B, Leitner E, and Pfannhauser W (1999) Determination of the nicotine content of various edible nightshades (Solanaceae) and their products and estimation of the associated dietary nicotine intake. J Agric Food Chem 47:3113-3120.
385. Sims DN, James R, and Christensen T (1999) Another death due to ingestion of Nicotiana glauca. J Forensic Sci 44:447-449.
386. Soloway SB (1976) Naturally occurring insecticides. Environ Health Perspect 14:109-117.
387. Sotaniemi EA, Lumme P, Arvela P, and Rautio A (1996) Age and CYP3A4 and CYP2A6 activities marked by the metabolism of lignocaine and coumarin in man. Therapie 51:363-366.
388. Sotaniemi EA, Rautio A, Backstrom M, Arvela P, and Pelkonen O (1995) CYP3A4 and CYP2A6 activities marked by the metabolism of lignocaine and coumarin in patients with liver and kidney diseases and epileptic patients. Br J Clin Pharmacol 39:71-76.
389. Stalhandske T and Slanina P (1982) Nicotyrine inhibits in vivo metabolism of nicotine without increasing its toxicity. Toxicol Appl Pharmacol 65:366-372.
390. Steenkamp PA, van Heerden FR, and van Wyk BE (2002) Accidental fatal poisoning by Nicotiana glauca: identification of anabasine by high performance liquid chromatography/photodiode array/mass spectrometry. Forensic Sci Int 127:208-217.
391. Stevens R (1994) Joint abuse liability review of nicotine nasal spray, in FDA Drug Abuse Advisory Committee Background Information (cited in NDA 18612).
392. Strassburg CP, Manns MP, and Tukey RH (1998) Expression of the UDP-glucuronosyltransferase 1A locus in human colon. Identification and characterization of the novel extrahepatic UGT1A8. J Biol Chem 273:8719-8726.
393. Strassburg CP, Strassburg A, Nguyen N, Li Q, Manns MP, and Tukey RH (1999) Regulation and function of family 1 and family 2 UDP- glucuronosyltransferase genes (UGT1A, UGT2B) in human oesophagus. Biochem J 338:489-498.
394. Su T, Bao Z, Zhang QY, Smith TJ, Hong JY, and Ding X (2000) Human cytochrome P450 CYP2A13: predominant expression in the respiratory tract and its high efficiency metabolic activation of a tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Cancer Res 60:5074-5079.
395. Sugihara K, Kitamura S, and Tatsumi K (1996) S-(-)-Nicotine-1′-N- oxide reductase activity of rat liver aldehyde oxidase. Biochem Mol Biol Int 40:535-541.
396. Sullivan JP, Donnelly-Roberts D, Briggs CA, Anderson DJ, Gopalakrishnan M, Xue IC, Piattoni-Kaplan M, Molinari E, Campbell JE, McKenna DG, et al. (1997) ABT-089 [2-methyl-3-(2-(S)-pyrrolidinylmethoxy)pyridinel: I. A potent and selective cholinergic channel modulator with neuroprotective properties. J Pharmacol Exp Ther 283:235-246.
397. Sutherland G, Russell MA, Stapleton J, Feyerabend C, and Ferno O (1992) Nasal nicotine spray: a rapid nicotine delivery system. Psychopharmacology (Berl) 108:512-518.
398. Taavitsainen P, Juvonen R, and Pelkonen O (2001) In vitro inhibition of cytochrome P450 enzymes in human liver microsomes by a potent CYP2A6 inhibitor, trans-2-phenylcyclopropylamine (tranylcypromine) and its nonamine analog, cyclopropylbenzene. Drug Metab Dispos 29:217-222.
399. Takami K, Saito H, Okuda M, Takano M, and Inui KI (1998) Distinct characteristics of transcellular transport between nicotine and tetraethylammonium in LLC-PK1 cells. J Pharmacol Exp Ther 286:676-680.
400. Tassaneeyakul W, Guo LQ, Fukuda K, Ohta T, and Yamazoe Y (2000) Inhibition selectivity of grapefruit juice components on human cytochromes P450. Arch Biochem Biophys 378:356-363.
401. Tateishi T, Nakura H, Asoh M, Watanabe M, Tanaka M, Kumai T, Takashima S, Imaoka S, Funae Y, Yabusaki Y, et al. (1997) A comparison of hepatic cytochrome P450 protein expression between infancy and postinfancy. Life Sci 61:2567-2574.
402. Thompson MA, Moon E, Kim UJ, Xu J, Siciliano MJ, and Weinshilboum RM (1999) Human indolethylamine N-methyltransferase: cDNA cloning and expression, gene cloning and chromosomal localization. Genomics 61:285-297.
403. Tilashalski K, Rodu B, and Mayfield C (1994) Assessing the nicotine content of smokeless tobacco products. J Am Dent Assoc 125:590-592:594.
404. Tomizawa M and Casida JE (2003) Selective toxicity of neonicotinoids attributable to specificity of insect and mammalian nicotinic receptors. Annu Rev Entomol 48:339-364.
405. Tsai MC and Gorrod JW (1999) Evidence for the biosynthesis of A glucuronide conjugate of (S)-(-)-nicotine, but not (S)-(-)-cotinine or (+/-)-trans-3′-hydroxycotinine by marmoset hepatic microsomes. Drug Metab Drug Interact 15:223-237.
406. Turner JA, Sillett RW, and McNicol MW (1977) Effect of cigar smoking on carboxyhaemoglobin and plasma nicotine concentrations in primary pipe and cigar smokers and ex-cigarette smokers. Br Med J 2:1387-1389.
407. Tyndale RF and Sellers EM (2001) Variable CYP2A6-mediated nicotine metabolism alters smoking behavior and risk. Drug Metab Dispos 29:548-552.
408. Tyndale RF and Sellers EM (2002) Genetic variation in CYP2A6-mediated nicotine metabolism alters smoking behavior. Ther Drug Monit 24:163-171.
409. Tyroller S, Zwickenpflug W, and Richter E (2002) New sources of dietary myosmine uptake from cereals, fruits, vegetables and milk. J Agric Food Chem 50:4909-4915.
410. Ueda A, Kakizaki S, Negishi M, and Sueyoshi T (2002) Residue threonine 350 confers steroid hormone responsiveness to the mouse nuclear orphan receptor CAR. Mol Pharmacol 61:1284-1288.
411. Ujjin P, Satarug S, Vanavanitkun Y, Daigo S, Ariyoshi N, Yamazaki H, Reilly PE, Moore MR, and Kamataki T (2002) Variation in coumarin 7-hydroxylase activity associated with genetic polymorphism of cytochrome P450 2A6 and the body status of iron stores in adult Thai males and females. Pharmacogenetics 12:241-249.
412. Urakami Y, Akazawa M, Saito H, Okuda M, and Inui K (2002) cDNA cloning, functional characterization and tissue distribution of an alternatively spliced variant of organic cation transporter hOCT2 predominantly expressed in the human kidney. J Am Soc Nephrol 13:1703-1710.
413. Urakami Y, Okuda M, Masuda S, Saito H, and Inui KI (1998) Functional characteristics and membrane localization of rat multispecific organic cation transporters, OCT1 and OCT2, mediating tubular secretion of cationic drugs. J Pharmacol Exp Ther 287:800-805.
414. Urakawa N, Nagata T, Kudo K, Kimura K, and Imamura T (1994) Simultaneous determination of nicotine and cotinine in various human tissues using capillary gas chromatography/mass spectrometry. Int J Legal Med 106:232-236.
415. USDHHS (U.S. Department of Health and Human Services) (2000) Reducing tobacco use: a report of the surgeon general. Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, Atlanta, GA.
416. USDHHS (U.S. Department of Health and Human Services) (2001) Risks associated with smoking cigarettes with low machine-measured yields of tar and nicotine, in Smoking and Tobacco Control Monographs, Public Health Service, National Institutes of Health, National Cancer Institute, Bethesda, MD.
417. Vahakangas K and Pelkonen O (1993) Extrahepatic metabolism of nicotine and related compounds by P-450, in Nicotine and Related Alkaloids: Absorption-Distribution-Metabolism-Excretion (Gorrod JW and Wahren J eds) pp 111-127, Chapman & Hall, London.
418. Vernier JM, Holsenback H, Cosford ND, Whitten JP, Menzaghi F, Reid R, Rao TS, Sacaan AI, Lloyd GK, Suto CM, et al. (1998) Conformationally restricted analogues of nicotine and anabasine. Bioorg Med Chem Lett 8:2173-2178.
419. Villeneuve L, Girard H, Fortier LC, Gagne JF, and Guillemette C (2003) Novel functional polymorphisms in the UGT1A7 and UGT1A9 glucuronidating enzymes in Caucasian and African-American subjects and their impact on the metabolism of 7-ethyl-10-hydroxycamptothecin and flavopiridol anticancer drugs. J Pharmacol Exp Ther 307:117-128.
420. Voncken P, Rustemeier K, and Schepers G (1990) Identification of cis-3′-hydroxycotinine as a urinary nicotine metabolite. Xenobiotica 20:1353-1356.
421. Von Richter O, Pitarque M, Rodriguez-Antona C, Testa A, Mantovani R, Oscarson M, and Ingelman-Sundberg M (2004) Polymorphic NF-Y dependent regulation of human nicotine C-oxidase (CYP2A6). Pharmacogenetics 14:369-379.
422. Wada E, Bowman ER, Turnbull LB, and McKennis H Jr (1961) Norcotinine (desmethylcotinine) as a urinary metabolite of nornicotine. J Med Pharm Chem 4:21-30.
423. Wagenknecht LE, Cutter GR, Haley NJ, Sidney S, Manolio TA, Hughes GH, and Jacobs DR (1990) Racial differences in serum cotinine levels among smokers in the Coronary Artery Risk Development in (Young) Adults study. Am J Public Health 80:1053-1056.
424. Wald NJ, Idle M, Boreham J, and Bailey A (1981) Serum cotinine levels in pipe smokers: evidence against nicotine as cause of coronary heart disease. Lancet 2:775-777.
425. Wald NJ, Idle M, Boreham J, Bailey A, and Van Vunakis H (1984) Urinary nicotine concentrations in cigarette and pipe smokers. Thorax 39:365-368.
426. Wang H, Faucette SR, Gilbert D, Jolley SL, Sueyoshi T, Negishi M, and LeCluyse EL (2003a) Glucocorticoid receptor enhancement of pregnane X receptor-mediated CYP2B6 regulation in primary human hepatocytes. Drug Metab Dispos 31:620-630.
427. Wang H, Tan W, Hao B, Miao X, Zhou G, He F, and Lin D (2003b) Substantial reduction in risk of lung adenocarcinoma associated with genetic polymorphism in CYP2A13, the most active cytochrome P450 for the metabolic activation of tobacco-specific carcinogen NNK. Cancer Res 63:8057-8061.
428. Watt AP, Hitzel L, Morrison D, and Locker KL (2000) Determination of the in vitro metabolism of (+)- and (-)-epibatidine. J Chromatogr A 896:229-238.
429. West R, Hajek P, Foulds J, Nilsson F, May S, and Meadows A (2000) A comparison of the abuse liability and dependence potential of nicotine patch, gum, spray and inhaler. Psychopharmacology (Berl) 149:198-202.
430. Wiener D, Fang JL, Dossett N, and Lazarus P (2004) Correlation between UDP-glucuronosyltransferase genotypes and 4-(methylnitrosammo)-1-(3-pyridyl)-1- butanone glucuronidation phenotype in human liver microsomes. Cancer Res 64:1190-1196.
431. Willers S, Skarping G, Dalene M, and Skerfving S (1995) Urinary cotinine in children and adults during and after semiexperimental exposure to environmental tobacco smoke. Arch Environ Health 50:130-138.
432. Williams DE, Ding XX, and Coon MJ (1990a) Rabbit nasal cytochrome P-450 NMa has high activity as a nicotine oxidase. Biochem Biophys Res Commun 168:945-952.
433. Williams DE, Shigenaga MK, and Castagnoli N Jr (1990b) The role of cytochromes P-450 and flavin-containing monooxygenase in the metabolism of (S)-nicotine by rabbit lung. Drug Metab Dispos 18:418-428.
434. Wu X, George RL, Huang W, Wang H, Conway SJ, Leibach FH, and Ganapathy V (2000) Structural and functional characteristics and tissue distribution pattern of rat OCTN1, an organic cation transporter, cloned from placenta. Biochim Biophys Acta 1466:315-327.
435. Xia XY, Peng KX, Yu JP, Wang H, and Wang J (2002) In vitro metabolic characteristics of cytochrome P-450 2A6 in Chinese liver microsomes. Acta Pharmacol Sin 23:471-476.
436. Xu C, Goodz S, Sellers EM, and Tyndale RF (2002a) CYP2A6 genetic variation and potential consequences. Adv Drug Deliv Rev 54:1245-1256.
437. Xu C, Rao YS, Xu B, Hoffmann E, Jones J, Sellers EM, and Tyndale RF (2002b) An in vivo pilot study characterizing the new CYP2A6*7, *8 and *10 alleles. Biochem Biophys Res Commun 290:318-324.
438. Xu P, Huang SL, Zhu RH, Han XM, and Zhou HH (2002c) Phenotypic polymorphism of CYP2A6 activity in a Chinese population. Eur J Clin Pharmacol 58:333-337.
439. Yabuuchi H, Tamai I, Nezu J, Sakamoto K, Oku A, Shimane M, Sai Y, and Tsuji A (1999) Novel membrane transporter OCTN1 mediates multispecific, bidirectional and pH-dependent transport of organic cations. J Pharmacol Exp Ther 289:768-773.
440. Yamano S, Tatsuno J, and Gonzalez FJ (1990) The CYP2A3 gene product catalyzes coumarin 7-hydroxylation in human liver microsomes. Biochemistry 29:1322-1329.
441. Yamazaki H, Inoue K, Hashimoto M, and Shimada T (1999) Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol 73:65-70.
442. Yang M, Kunugita N, Kitagawa K, Kang SH, Coles B, Kadlubar FF, Katoh T, Matsuno K, and Kawamoto T (2001) Individual differences in urinary cotinine levels in Japanese smokers: relation to genetic polymorphism of drug-metabolizing enzymes. Cancer Epidemiol Biomarkers Prev 10:589-593.
443. Yi JM, Sprouse CT, Bowman ER, and McKennis H Jr (1977) The interrelationship between the metabolism of (S)-cotinine-N-oxide and (S)-cotinine. Drug Metab Dispos 5:355-362.
444. Yoshida R, Nakajima M, Nishimura K, Tokudome S, Kwon JT, and Yokoi T (2003) Effects of polymorphism in promoter region of human CYP2A6 gene (CYP2A6*9) on expression level of messenger ribonucleic acid and enzymatic activity in vivo and in vitro. Clin Pharmacol Ther 74:69-76.
445. Yoshida R, Nakajima M, Watanabe Y, Kwon JT, and Yokoi T (2002) Genetic polymorphisms in human CYP2A6 gene causing impaired nicotine metabolism. Br J Clin Pharmacol 54:511-517.
446. Zeman MV, Hiraki L, and Sellers EM (2002) Gender differences in tobacco smoking: higher relative exposure to smoke than nicotine in women. J Womens Health Gend Based Med 11:147-153.
447. Zevin S and Benowitz NL (1999) Drug interactions with tobacco smoking. An update. Clin Pharmacokinet 36:425-438.
448. Zevin S, Jacob P 3rd, and Benowitz N (1997) Cotinine effects on nicotine metabolism. Clin Pharmacol Ther 61:649-654.
449. Zevin S, Jacob P 3rd, and Benowitz NL (2000a) Nicotine-mecamylamine interactions. Clin Pharmacol Ther 68:58-66.
450. Zevin S, Jacob P, Geppetti P, and Benowitz NL (2000b) Clinical pharmacology of oral cotinine. Drug Alcohol Depend 60:13-18.
451. Zhang W, Kilicarslan T, Tyndale RF, and Sellers EM (2001) Evaluation of methoxsalen, tranylcypromine and tryptamine as specific and selective CYP2A6 inhibitors in vitro. Drug Metab Dispos 29:897-902.
452. Zhang X, Ameno K, Ameno S, Kinoshita H, Kubota T, Kumihashi M, Mostofa J, Iwahashi K, and Ijiri I (2002) Effects of whole deletion of CYP2A6 on nicotine metabolism in humans. Drug Chem Toxicol 25:203-213.
453. Zhang X, Chen Y, Liu Y, Ren X, Zhang QY, Caggana M, and Ding X (2003) Single nucleotide polymorphisms of the human cyp2a13 gene: evidence for a null allele. Drug Metab Dispos 31:1081-1085.
454. Zheng Z, Fang JL, and Lazarus P (2002) Glucuronidation: an important mechanism for detoxification of benzotalpyrene metabolites in aerodigestive tract tissues. Drug Metab Dispos 30:397-403.
455. Zins BJ, Sandborn WJ, Mays DC, Lawson GM, McKinney JA, Tremaine WJ, Mahoney DW, Zinsmeister AE, Hurt RD, Offord KP, and Lipsky JJ (1997) Pharmacokinetics of nicotine tartrate after single-dose liquid enema, oral and intravenous administration. J Clin Pharmacol 37:426-436.
456. Zwickenpflug W, Meger M, and Richter E (1998) Occurrence of the tobacco alkaloid myosmine in nuts and nut products of Arachus hypogaea and Corylus avellana. J Agric Food Chem 46:2703-2706.