Relevance of induction of human drug-metabolizing enzymes: Pharmacological and toxicological implications

British Journal of Clinical Pharmacology

Volumn 41, Issue 6, 1996, Pages 477-491

  Park, B K ^a   Kitteringham, N R ^a   Pirmohamed, M ^a   Tucker, G T ^b  

^a UNIVERSITY OF LIVERPOOL   (United Kingdom)

^b ROYAL HALLAMSHIRE HOSPITAL   (United Kingdom)

Author keywords

c learance; cytochrome P450; drug metabolism; enzyme induction; glucuronidation; human; liver; pharmacodynamics; pharmacokinetics; toxicity

Indexed keywords

ALCOHOL DEHYDROGENASE; ANTICONVULSIVE AGENT; AROMATIC HYDROCARBON RECEPTOR; CARBAMAZEPINE; CYTOCHROME P450; DAPSONE; DRUG METABOLIZING ENZYME; ENZYME INDUCING AGENT; ETHINYLESTRADIOL; FELODIPINE; GLUCURONOSYLTRANSFERASE; GLUTATHIONE TRANSFERASE; LAMOTRIGINE; NORETHISTERONE; OLTIPRAZ; OMEPRAZOLE; ORAL CONTRACEPTIVE AGENT; OXCARBAZEPINE; PARACETAMOL; PHENOBARBITAL; PHENYTOIN; RIFAMPICIN; TACRINE; VALPROIC ACID; VALPROMIDE; VIGABATRIN;

AREA UNDER THE CURVE; CIGARETTE SMOKING; CLINICAL TRIAL; DRUG CLEARANCE; DRUG DETOXIFICATION; DRUG HYPERSENSITIVITY; DRUG METABOLISM; DRUG OVERDOSE; ENZYME INDUCTION; HEPATITIS; HUMAN; METHEMOGLOBINEMIA; MICHAELIS CONSTANT; NONHUMAN; ORAL DRUG ADMINISTRATION; PRIORITY JOURNAL; REVIEW; ERRATUM; ERROR;

EID: 0029885913     PISSN: 03065251     EISSN: None     Source Type: Journal    
DOI: 10.1046/j.1365-2125.1996.03482.x     Document Type: Review

References (135)

1. Price DE, Mehta A, Park BK, Hay A, Feely MP. The effect of low-dose phenobarbitone on three indices of hepatic microsomal enzyme induction. Br J Clin Pharmacol 1986; 22: 744-747.
2. Park BK, Breckenridge AM. Clinical implications of enzyme induction and enzyme inhibition. Clin Pharmacokinet 1981; 6: 1-24.
3. Park BK, Kitteringham NR. Relevance of and means of assessing induction and inhibition of drug metabolism in man. In Progress in Drug Metabolism, ed Gibson GG, London: Taylor and Francis, 1989: 1-60.
4. Rost KL, Roots I. Accelerated caffeine metabolism after omeprazole treatment is indicated by urinary metabolite ratios: coincidence with plasma clearance and breath test. Clin Pharmacol Ther 1994; 55: 402-411.
5. Horsmans Y, Deager JP, Van den Berge V, Abrassart M, Harvengt C. Effects of simvastatin and pravastatin on 6β-hydroxycortisol excretion a potential marker of cytochrome P-450 3A. Pharmacol Res 1993; 28: 243-247.
6. Gonzalez FJ. The molecular biology of cytochrome P450s. Pharmacol Rev 1988; 40: 243-288.
7. Hanioka N, Jinno H, Takahashi A, et al. Interaction of tetrachloroethylene with rat hepatic microsomal P450-dependent monooxygenases. Xenobiotica 1995; 25: 151-167.
8. Kalow W, Tang B-K. Use of caffeine metabolic ratios to explore CYP1A2 and xanthine oxidase activities. Clin Pharmacol Ther 1991; 50: 508-519.
9. Back DJ, Tjia J, Moenig H, Ohnhaus EE, Park BK. Selective inhibition of drug oxidation after simultaneous administration of two probe drugs, antipyrine and tolbutamide. Eur J Clin Pharmacol 1988; 34: 157-163.
10. Wright JD, Helsby NA, Ward SA. The role of S-mephenytoin hydroxylase (CYP2C19) in the metabolism of the antimalarial biguanides. Br J Clin Pharmacol 1995; 39: 441-444.
11. Helsby NA, Edwards G, Breckenridge AM, Ward SA. The multiple-dose pharmacokinetics of proguanil. Br J Clin Pharmacol 1993; 35: 653-656.
12. Eichelbaum M, Spannbrucker N, Steincke B, Dengler HJ. Defective N-oxidation of sparteine in man, a new pharmacogenetic defect. Eur J Clin Pharmacol 1979; 16: 183-187.
13. Larrey D, Berson A, Habersetzer F, et al. Genetic predisposition to drug hepatotoxicity: role in hepatitis caused by amineptine, a tricyclic antidepressant. Hepatology 1989; 10: 168-173.
14. Dreisbach AW, Ferencz N, Hopkins NE, et al. Urinary excretion of 6-hydroxychlorzoxazone as an index of CYP2E1 activity. Clin Pharmacol Ther 1995; 58: 498-505.
15. Watkins PB, Hamilton TA, Annesley TM, Ellis CN, Kolars JC, Voorhees JJ. The erythromycin breath test as a predictor of cyclosporine blood levels. Clin Pharmacol Ther 1990; 48: 120-129.
16. Thummel KE, Shen DD, Podoll TD, et al. Use of midazolam as a human cytochrome P450 3A probe .1. In vitro-in vivo correlations in liver transplant patients. J Pharmacol Exp Ther 1994; 271: 549-556.
17. Ged C, Rouillon JM, Pichard L, et al. The increase in urinary excretion of 6 beta-hydroxycortisol as a marker of human hepatic cytochrome P450II1A induction. Br J Clin Pharmacol 1989; 28: 373-387.
18. Kroetz DL, Kerr BM, McFarland LV, Loiseau P, Wilensky AJ, Levy RH. Measurement of in vivo microsomal epoxide hydrolase activity in white subjects. Clin Pharmacol Ther 1993; 53: 306-315.
19. Price Evans DA. N-acetyltransferase. Pharmac Ther 1989; 42: 157-234.
20. Grant DM, Tang BK, Kalow W. (1984) A simple test for acetylator phenotype using caffeine. Br J Clin Pharmacol 1984; 17: 459-464.
21. Scott AK, Khir ASM, Steele WH, Hawksworth GM, Petrie JC. Oxazepam pharmacokinetics in patients with epilepsy treated long-term with phenytoin alone or in combination with phenobarbitone. Br J Clin Pharmacol 1983; 16: 441-444.
22. Gonzalez FJ, Liu SY, Yano M. Regulation of cytochrome P-450 genes:molecular mechanisms. Pharmacogenetics 1993; 3: 51-57.
23. Ronis MJJ, Huang JA, Crouch J, et al. Cytochrome-P450 CYP-2E1 induction during chronic alcohol exposure occurs by a 2-step mechanism associated with blood-alcohol concentrations in rats. J Pharmacol Exp Ther 1993; 264: 944-950.
24. Song BJ, Veech RL, Park SS, Gelboin HV, Gonzalez FJ. Induction of rat hepatic nitrosodimethylaniline demethylase by acetone is due to protein stabilisation. J Biol Chem 1989; 264: 3568-3572.
25. Takahashi T, Lasker JM, Rosman AS, Lieber CS. Induction of cytochrome P-4502E1 in the human liver by ethanol is caused by a corresponding increase in encoding messenger RNA. Hepatology 1993; 17: 236-245.
26. Eliasson E, Mkrtchian S, Halpert JR, Ingelman-Sundberg M. (1994) Substrate-regulated, cAMP-dependent phosphorylation, denaturation, and degradation of glucocorticoid-inducible rat-liver cytochrome-P450 3A1. J Biol Chem 1994; 269: 18378-18383.
27. Roberts BJ, Shoaf SE, Song BJ. Rapid changes in cytochrome P4502E1 (CYP2E1) activity and other P450 isozymes following ethanol withdrawal in rats. Biochem Pharmacol 1995; 49: 1665-1673.
28. Koop DR. Degradation of P4502E1. Signals for degradation and the proteolytic pathway. Microsomes Meeting abstract, Toronto, Canada, 1994: 96-98.
29. Eliasson E, Johansson I, Ingelman-Sundberg M. Substrate-regulated, hormone-regulated, and cAMP-regulated cytochrome P450 degradation. Proc Natl Acad Sci (USA) 1990; 87: 3225-3229.
30. Thomas PE, Reik LM, Ryan DE. Induction of two immunochemically related rat liver cytochrome P-450 isozymes, cytochrome P-450c and P-450d, by structurally diverse xenobiotics. J Biol Chem 1983; 258: 4590-4598.
31. Poland A, Glover E, Kende AS. Stereospecific high affinity binding of 2,3,7,8-tetrachloro-p-dioxin by hepatic cytosol. Evidence that the binding species is the receptor for induction of arylhydrocarbon hydroxylase. J Biol Chem 1976; 251: 4936-4946.
32. Dolwick KM, Schnidt JV, Carver LA, Swanson HI, Bradfield CA. Cloning and expression of a human Ah receptor cDNA. Mol Pharmacol 1973; 44: 911-917.
33. Nebert DW, Puga A, Vasiliou V. Role of the Ah receptor and the dioxin-inducible [Ah] gene battery in toxicity, cancer, and signal-transduction. Ann N Y Acad Sci 1993; 685: 624-640.
34. Whitlock JP. Mechanistic aspects of dioxin action. Chem Res Toxicol 1993; 6: 754-763.
35. Fernandez-Salguero P, Pineau T, Hilbert DM, et al. Immune-system impairment and hepatic-fibrosis in mice lacking the dioxin-binding Ah receptor. Science 1995; 268: 722-726.
36. Waxman DJ, Arzaroff L. Phenobarbital induction of cytochrome P-450 gene expression. Biochem J 1992; 281: 577-592.
37. He JS, Fulco AJ. A barbiturate-regulated protein-binding to a common sequence in the cytochrome-P450 genes of rodents and bacteria. J Biol Chem 1991; 266: 7864-7869.
38. Liang QW, He JS, Fulco AJ. The role of Barbie box sequences as cis-acting elements involved in the barbiturate-mediated induction of cytochromes P450(BM-1) and P450(BM-3) in Bacillus-megaterium. J Biol Chem 1995; 270: 4438-4450.
39. Shaw GC, Fulco AJ. Inhibition by barbiturates of the binding of BM3R1 repressor to its operator site on the barbiturate-inducible cytochrome-P450(BM-3) gene of Bacillus-megaterium. J Biol Chem 1993; 268: 2997-3004.
40. Shou M, Grogan J, Mancewicz JA, et al. Activation of CYP3A4: Evidence for the simultaneous binding of two substrates in a cytochrome P450 active site. Biochemistry 1994; 33: 6450-6455.
41. Mulder GJ. Glucuronidation and its role in regulation of biological activity of drugs. Ann Rev Pharmacol Toxicol 1992; 32: 25-49.
42. Burchell B, Nebert DW, Nelson DR, et al. The UDP glucuronosyltransferase gene superfamily: suggested nomenclature based on evolutionary divergence. DNA Cell Biol 1991; 10:487-494.
43. Binnie CD, van Emde Boas W, Kasteleijn-Nolste-Trenite DG, et al. Acute effects of lamotrigine (BW430C) in persons with epilepsy. Epilepsia 1986; 27: 248-254.
44. Jawad S, Yuen WC, Peck AW, Hamilton MJ, Oxley JR, Richens A. Lamotrigine-single-dose pharmacokinetics and initial 1 week experience in refractory epilepsy. Epilepsy Res 1987; 1: 194-201.
45. Brodie MJ. Lamotrigine. Lancet 1992; 339: 1397-1400.
46. Bosma PJ, Chowdhury NR, Goldhoorn BG, et al. Sequence of exons and the flanking regions of human bilirubin-UDP-glucuronosyltransferase gene complex and identification of a genetic mutation in a patient with Crigler-Najjar syndrome, type I. Hepatology 1992; 15: 941-947.
47. Bosma PJ, Chowdhury JR, Jansen PHM. Genetic inheritance of Gilbert's-syndrome. Lancet 1995; 346: 314-315.
48. De Morais SMF, Uetrecht JP, Wells PG. Decreased glucuronidation and increased bioactivation of acetaminophen in Gilbert's syndrome. Gastroenterology 1992; 102: 577-586.
49. Peck AW. Clinical pharmacology of lamotrigine. Epilepsia 1991; 32(Suppl. 2): S9-S12.
50. Capewell S, Critchley JAJH, Freestone S, Pottage A. Reduced felodipine bioavailability in patients taking anticonvulsants. Lancet 1988; ii: 480-482.
51. Pirmohamed M, Allot R, Green VJ, Kitteringham NR, Chadwick D, Park BK. Lymphocyte microsomal epoxide hydrolase in patients on carbamazepine therapy. Br J Clin Pharmacol 1994; 37: 577-581.
52. Back DJ, Maggs JL, Purba HS, Newby S, Park BK. 2-Hydroxylation of ethinylestradiol in relation to the oxidation of sparteine and antipyrine. Br J Clin Pharmacol 1984; 18: 603-607.
53. Maggs JL, Park BK. A comparative study of biliary and urinary 2-hydroxylated metabolites of [6,7-3H]17α-ethinylestradiol in women. Contraception 1985; 32: 173-182.
54. Back DJ, Orme ML'E. Drug interactions. In Pharmacology of the contraceptive steroids, ed Goldzieher JW, New York: Raven Press, 1994: 407-425.
55. Bolt HM, Kappus H, Kasbohrer R. Metabolism of 17α-ethinyloestradiol by human liver microsomes in vitro: Aromatic hydroxylation and irreversible protein binding of metabolites. J Clin Endocrinol Metab 1974; 39: 1072-1080.
56. Ohnhaus EE, Park BK. The measurement of 6β-hydroxycortisol urinary excretion as an in vivo parameter in the clinical assessment of the microsomal enzyme inducing capacity of antipyrine, phenobarbitone and rifampicin. Eur J Clin Pharmacol 1979; 15: 139.
57. Kanarkowski R, Tornatore KM, D'Ambrosio R, Gardner MJ, Jusko WJ. Pharmacokinetics of single and multiple doses of ethinylestradiol and levonorgestrel in relation to smoking. Clin Pharmacol Ther 1988; 43: 23-31.
58. Michnovicz JJ, Hershcopf RJ, Naganuma H, Bradlow HL, Fishman J. Increased 2-hydroxylation of estradiol as a possible mechanism for the anti-estrogenic effect of cigarette-smoking. N Engl J Med 1986; 315: 1305-1309.
59. Guengerich FP. Oxidation of 17α-ethynylestradiol by human liver cytochrome P-450. Mol Pharmacol 1988; 33: 500-508.
60. Diaz D, Fabre I, Daujat M, et al. Omeprazole is an aryl hydrocarbon-like inducer of hepatic cytochrome P-450. Gastroenterology 1990; 99: 737-747.
61. Buchthal J, Grund KE, Buchmann A, Schenk D, Beaune P, Bock KW. Induction of cytochrome P4501A by smoking or omeprazole in comparison with glucuronyltransferase in biopsies of human duodenal mucosa. Eur J Clin Pharmacol 1995; 47: 431-435.
62. Rost KL, Brosicke H, Heinemeyer G, Roots I. Specific and dose-dependent enzyme induction by omeprazole in human beings. Hepatology 1994; 20: 1204-1212.
63. Xiaodong S, Gatti G, Bartoli A, Cipolla G, Crema F, Perruca E. Omeprazole does not enhance the metabolism of phenacetin, a marker of CYP1A2 activity in healthy volunteers. Ther Drug Monit 1994; 16: 248-250.
64. Brodie MJ. Drug-interactions in epilepsy. Epilepsia 1992; 33: s13-s22.
65. Jawad S, Yuen WC, Peck AW, Hamilton MJ, Oxley J, Richens A. Lamotrigine: single dose pharmacokinetics and initial one week experience in refractory epilepsy. Epilepsy Res 1987; 1: 194-201.
66. Pirmohamed M, Kitteringham NR, Park BK. The role of active metabolites in drug toxicity. Drug Safety 1994; 11: 114-144.
67. Yuen AWC, Land G, Weatherley BC, Peck AW. Sodium valproate acutely inhibits lamotrigine metabolism. Br J Clin Pharmacol 1992; 33: 511-513.
68. Kerr BM, Rettie AE, Eddy C, et al. Inhibition of human liver microsomal epoxide hydrolase by valproate and valpromide: in vitro/in vivo correlation. Clin Pharmacol Ther 1989; 46: 82-93.
69. Warner T, Patsalos PN, Prevett M, Elyas AA, Duncan JS. Lamotrigine-induced carbamazepine toxicity: an interaction with carbamazepine-10,11-epoxide. Epilepsy Res 1992; 11: 147-150.
70. Hebert MF, Roberts JP, Prueksaritanont T, Benet LZ. Bioavailability of cyclosporine with concomitant rifampin administration is markedly less than predicted by enzyme induction. Clin Pharmacol Ther 1992; 52: 453-457.
71. Seeff LB, Cuccherini BA, Zimmerman HJ, Adler E, Benjamin SB. Acetaminophen hepatotoxicity in alcoholics. A therapeutic misadventure. Ann Intern Med 1986; 104: 399-404.
72. Bray GP, Mowat C, Muir DF, Tredger JM, Williams R. The effect of chronic alcohol intake on prognosis and outcome in paracetamol overdose. Human Exp Toxicol 1991; 10: 435-438.
73. Nelson SD. Molecular mechanisms of the hepatotoxicity caused by acetaminophen. Semin Liver Dis 1990; 10: 267-278.
74. Thummel KE, Lee CA, Kunze KL, Nelson SD, Slattery JT. Oxidation of acetaminophen to N-acetyl-p-aminobenzoquinone imine by human CYP3A4. Biochem Pharmacol 1993; 45: 1563-1569.
75. Dai Y, Cederbaum AI. Cytoxicity of acetaminophen in human cytochrome P4502E1-transfected HepG2 cells. J Pharmacol Exp Ther 1995; 273: 1497-1505.
76. Whitcomb DC, Block GD. Association of acetaminophen hepatotoxicity with fasting and ethanol use. JAMA 1994; 272: 1845-1850.
77. Nanji AA, Zhao S, Khaja S, Sadrzadeh SMH, Waxman DJ. Cimetidine prevents alcoholic hepatic injury in the intragastric feeding rat model. J Pharmacol Exp Ther 1994; 269: 832-837.
78. Ingelman-Sundberg M, Johansson I, Penttila KE, Glaumann H, Lindros KO. Centrilobular expression of ethanol-inducible cytochrome P-450 (IIE1) in rat liver. Biochem Biophys Res Commun 1988; 157: 55-60.
79. Zimmerman HJ, Maddrey WC. Acetaminophen (paracetamol) hepatotoxicity with regular intake of alcohol - analysis of instances of therapeutic misadventure. Hepatology 1995; 22: 767-773.
80. Bray GP, Harrison PM, O'Grady JG, Tredger JM, Williams R. Long-term anticonvulsant therapy worsens outcome in paracetamol-induced fulminant hepatic failure. Human Exp Toxicol 1992; 11: 265-270.
81. Miners JO, Attwood J, Birkett DJ. Determinants of acetaminophen metabolism: Effect of inducers and inhibitors of drug metabolism on acetaminophen's metabolic pathways. Clin Pharmacol Ther 1984; 35: 480-486.
82. Guengerich FP, Kim DY, Iwasaki M. Role of human cytochrome P-450IIE1 in the oxidation of many low molecular weight cancer suspects. Chem Res Toxicol 1991; 4: 168-179.
83. Koop DR. Oxidative and reductive metabolism by cytochrome P450 2E1. FASEB J 1992; 6: 724-730.
84. Tredger JM, Smith HM, Read RB, Portmann B, Williams R. Effects of ethanol ingestion on the metabolism of a hepatotoxic dose of paracetamol in mice. Xenohiotica 1986; 16: 661-670.
85. Altomare E, Leo MA, Sato C, Vendemiale G, Lieber CS. Interaction of ethanol with acetaminophen metabolism in the baboon. Biochem Pharmacol 1984; 33: 2207-2212.
86. Perrot N, Nalpas B, Yang CS, Beaune PH. Modulation of cytochrome P450 isozymes in human liver, by ethanol and drug intake. Eur J Clin Invest 1989; 19: 549-555.
87. Girre C, Lucas D, Hispard E, Menez C, Dally S, Menez JF. Assessment of cytochrome P4502E1 induction in alcoholic patients by chlorzoxazone pharmacokinetics. Biochem Pharmacol 1994; 47: 1503-1508.
88. O'Shea D, Davis SN, Kim RB, Wilkinson GR. Effect of fasting and obesity in humans on the 6-hydroxylation of chlorzoxazone - a putative probe of CYP2E1 activity. Clin Pharmacol Ther 1994; 56: 359-367.
89. Day CP, Bassendine MF. Genetic predisposition to alcoholic liver disease. Gut 1992; 33: 1444-1447.
90. Brunt PW, Kew MC, Scheuer PJ, Sherlock S. Studies in alcoholic liver disease in Britain. Gut 1974; 15: 52-58.
91. Clot P, Bellomo G, Tabone M, Arico S, Albano E. Detection of antibodies against proteins modified by hydroxyethyl free-radicals in patients with alcoholic cirrhosis. Gastroenterology 1995; 108: 201-207.
92. Albano E, Tomasi A, Persson J-O, et al. Role of ethanol-inducible cytochrome P-450 (P-450IIE1) in catalysis of the free radical activation of aliphatic alcohols. Biochem Pharmacol 1991; 41: 1895-1902.
93. Hayashi S, Watanabe J, Kawajiri K. Genetic polymorphisms in the 5′-flanking region change transcriptional regulation of the human cytochrome P450IIE1 gene. J Biochem (Tokyo) 1991; 110: 559-565.
94. Pirmohamed M, Kitteringham NR, Quest LJ, et al. Genetic polymorphism of cytochrome P4502E1 and risk of alcoholic liver disease in Caucasians. Pharmacogenetics 1995; 5: 351-357.
95. Pohl LR, Kenna JG, Satoh H, Christ D. Neoantigens associated with halothane hepatitis. Drug Metab Rev 1989; 20: 203-217.
96. Gut J, Christen U, Huwyler J. Mechanisms of halothane toxicity: novel insights. Pharmacol Ther 1993; 58: 133-155.
97. Mazze RI, Trudell JR, Cousins MJ. Methoxyflurane metabolism and renal disfunction. Anesthesiology 1971; 35: 247-252.
98. Park BK, Kitteringham NR. Effects of fluorine substitution on drug-metabolism - pharmacological and toxicological implications. Drug Metab Rev 1994; 26: 605-643.
99. Mazze RI, Woodruff RE, Heerdt ME. Isoniazid-induced defluorination in humans. Anesthesiology 1982; 57: 5-8.
100. Gauntlett IS, Koblin DD, Fancy MR, et al. Metabolism of enflurane in patients receiving isoniazid. Anesth Analg 1989; 69: 245-249.
101. Dooley JR, Mazze RI, Rice SA, Borel JD. Is enflurane defluorination inducible in humans? Anesthesiology 1979; 50: 213-217.
102. Frink EJ. The hepatic-effects of sevoflurane. Anesth Analg 1995; 81: S46-S50.
103. Kharasch ED, Armstrong AS, Gunn K, Artru A, Cox K, Karol MD. Clinical sevoflurane metabolism and disposition .2. the role of cytochrome-P450 2E1 in fluoride and hexafluoroisopropanol formation. Anesthesiology 1995; 82: 1379-1388.
104. Watkins PB, Zimmerman HJ, Knapp MJ, Gracon SI, Lewis KW. Hepatotoxic effects of tacrine administration in patients with Alzheimer's disease. JAMA 1994; 271: 992-998.
105. Madden S, Spaldin V, Hayes RN, Woolf TF, Pool WF, Park BK. Species variation in the bioactivation of tacrine by hepatic microsomes. Xenobiotica 1995; 25: 103-116.
106. Spaldin V, Madden S, Adams DA, Edwards RJ, Davies DS, Park BK. Determination of human hepatic cytochrome P4501A2 activity in vitro: use of tacrine as an isozyme specific probe. Drug Metab Dispos 1995; 23: 929-934.
107. Prestera T, Zhang Y, Spencer SR, Wilczak CA, Talalay P. The electrophile counterattack response: protection against neoplasia and toxicity. Adv Enzyme Regul 1993; 33: 281-296.
108. Barker CW, Fagan JB, Pasco DS. Down-regulation of P4501A1 and P4501A2 mRNA expression in isolated hepatocytes by oxidative stress. J Biol Chem 1994; 269: 3985-3990.
109. Green VJ, Pirmohamed M, Kitteringham NR, Knapp MJ, Park BK. Glutathione S-transferase mu genotype (GSTM1*O) in Alzheimer's patients with tacrine transaminitis. Br J Clin Pharmacol 1995; 39: 411-415.
110. Anon. Teratogenesis with carbamazepine. Lancet 1991; 337: 1316-1317.
111. Shear NH, Spielberg SP, Cannon M, Miller M. Anticonvulsant hypersensitivity syndrome: in vitro risk assessment. J Clin Invest 1988; 82: 1826-1832.
112. Kaneko S, Otani K, Kondo T, et al. Malformation in infants of mothers with epilepsy receiving antiepileptic drugs. Neurology 1992; 42: 68-74.
113. Lertratanangkoon K, Horning MG. Metabolism of carbamazepine. Drug Metab Dispos 1982; 10: 1-10.
114. Pirmohamed M, Kitteringham NR, Guenthner TM, Breckenridge AM, Park BK. Investigation into the formation of cytotoxic, protein reactive and stable metabolites from carbamazepine in vitro. Biochem Pharmacol 1992; 43: 1675-1682.
115. Pirmohamed M, Graham A, Roberts P, et al. Carbamazepine hypersensitivity: assessment of clinical and in vitro chemical cross-reactivity with phenytoin and oxcarbazepine. Br J Clin Pharmacol 1991; 32: 741-749.
116. Guenthner TM, Kuk J, Nguyen M, Wheeler C, Pirmohamed M. Analysis of microsomal epoxide hydrolase levels in human tissues using monoclonal antibodies. FASEB J 1991; 5: A1570.
117. Davis C, Pirmohamed M, Kitteringham NR, Allott RL, Smith D, Park BK. Kinetic parameters of lymphocyte microsomal epoxide hydrolase in carbamazepine hypersensitive patients: assessment by radiometric HPLC. Biochem Pharmacol 1995; 9: 1361-1366.
118. Green VJ, Pirmohamed M, Kitteringham NR, et al. Genetic analysis of microsomal epoxide hydrolase in patients with carbamazepine hypersensitivity. Biochem Pharmacol 1995; 9: 1353-1359.
119. Gaedigk A, Spielberg SP, Grant DM. Characterization of the microsomal epoxide hydrolase gene in patients with anticonvulsant adverse drug-reactions. Pharmacogenetics 1994; 4: 142-153.
120. Green VJ, Pirmohamed M, Kitteringham NR, Brodie MJ, Park BK. Glutathione-S-transferase mu genotype (GSTM1*0) in patients with carbamazepine hypersensitivity. Br J Clin Pharmacol 1995; 39: 555P.
121. Anderson GD, Gidal BE, Kantor ED, Wilensky AJ. Lorazepam-valproate interaction - studies in normal subjects and isolated-perfused rat-liver. Epilepsia 1994; 35: 221-225.
122. McPhee GJA, Mitchell JR, Wiseman L, et al. Effect of sodium valproate on carbamazepine disposition and psychomotor profile in man. Br J Clin Pharmacol 1988; 25: 59-66.
123. Friedmann PS, Strickland I, Pirmohamed M, Park BK. Investigation of mechanisms in toxic epidermal necrolysis induced by carbamazepine. Arch Dermatol 1994; 130: 598-604.
124. Zuidema J, Hilbers-Moddermann ESM, Merkus FWHM. Clinical pharmacokinetics of dapsone. Clin Pharmacokinet 1986; 11: 299-315.
125. Kramer PA, Glader BE, Li TK. Mechanism of methaemoglobin formation by diphenylsulfones. Effect of 4-amino-4′-hydroxy-aminodiphenylsulfone and other p-substituted derivatives. Biochem Pharmacol 1972; 21: 1265-1274.
126. Fleming CM, Branch RA, Wilkinson GR, Guengerich FP. Human liver microsomal N-hydroxylation of dapsone by cytochrome P-4503A4. Mol Pharmacol 1992; 41: 975-980.
127. Mitra AK, Thummel KE, Kalhorn TF, Kharasch ED, Unadkat JD, Slattery JT. Metabolism of dapsone to its hydroxylamine by CYP2E1 in vitro and in vivo. Clin Pharmacol Ther 1995; 58: 556-566.
128. Gill HJ, Tingle MD, Park BK. N-hydroxylation of dapsone by multiple enzymes of cytochrome P450: implications for inhibition of haemotoxicity. Br J Clin Pharmacol 1995; 40: 531-539.
129. Occhipinti DJ, Choi A, Deyo K, Danziger LH, Fischer JH. Influence of rifampicin and clarithromycin on dapsone disposition and methemoglobin concentrations. Clin Pharmacol Ther 1995; 57: 163.
130. Prochaska HJ, Santamaria AB, Talalay P. Rapid detection of inducers that protect against carcinogens. Proc Natl Acad Sci (USA) 1992; 89: 2394-2398.
131. Zhang H, Zdolsek JM, Brunk UT. Alloxan cytotoxicity involves lysosomal damage. Apmis 1992; 100: 309-316.
132. Egner PA, Kensler PW, Prestera T, et al. Regulation of phase 2 enzyme-induction by oltipraz and other dithiolethiones. Carcinogenesis 1994; 15: 177-181.
133. McCain RM, Levin AA, Posch R, Downing JC. The effect of phenobarbital on the metabolism and excretion of thyroxine in rats. Toxicol Appl Pharmacol 1989; 99: 216-228.
134. Larkin JG, Macphee GJA, Beastall GH, Brodie MJ. Thyroid hormone concentrations in epileptic patients. Eur J Clin Pharmacol 1989; 36: 213-216.
135. Ohnhaus EE, Studer HA. Link between liver microsomal enzyme activity and thyroid hormone metabolism in man. Br J Clin Pharmacol 1983; 15: 71-76.