Pharmacogenetics of analgesics: Toward the individualization of prescription

Pharmacogenomics

Volumn 9, Issue 7, 2008, Pages 905-933

  Rollason, Victoria ^a   Samer, Caroline ^a   Piguet, Valerie ^a   Dayer, Pierre ^a   Desmeules, Jules ^a  

^a GENEVA UNIVERSITY HOSPITALS   (Switzerland)

Author keywords

opioid receptor; Acetaminophen; Catechol O methyltransferase; Cytochrome P450; Melanocortin 1 receptor; NMDA receptor antagonist; Nonsteroidal anti inflammatory drugs; Opioid; P glycoprotein; Pharmacogenetic; Polymorphism; UDP glucoronsyltransferase

Indexed keywords

ACETYLSALICYLIC ACID; ALFENTANIL; ANALGESIC AGENT; BUPRENORPHINE; CELECOXIB; CIPROFLOXACIN; CODEINE; CYCLOSPORIN A; DEXTROMETHORPHAN; DICLOFENAC; FENTANYL; FLURBIPROFEN; HYDROCODONE; IBUPROFEN; LEVOMETHADONE; LOPERAMIDE; LORNOXICAM; METHADONE; MORPHINE; NAPROXEN; NONSTEROID ANTIINFLAMMATORY AGENT; OXYCODONE; PACLITAXEL; PARACETAMOL; PETHIDINE; PIROXICAM; QUINIDINE; TENOXICAM; TRAMADOL; UNINDEXED DRUG; CARRIER PROTEIN; CYTOCHROME P450;

ANALGESIC ACTIVITY; APNEA; AREA UNDER THE CURVE; BRAIN INJURY; CLINICAL TRIAL; COMA; CONFUSION; CONSTIPATION; DEMETHYLATION; DIZZINESS; DOSE RESPONSE; DRUG ABSORPTION; DRUG ACCUMULATION; DRUG BLOOD LEVEL; DRUG CEREBROSPINAL FLUID LEVEL; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG DOSE COMPARISON; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG ELIMINATION; DRUG EXPOSURE; DRUG HALF LIFE; DRUG MEGADOSE; DRUG METABOLISM; DRUG OVERDOSE; DRUG POTENCY; DRUG POTENTIATION; EPIGASTRIC PAIN; EUPHORIA; GASTROINTESTINAL HEMORRHAGE; GENE MUTATION; GENETIC POLYMORPHISM; HEREDITY; HUMAN; LIVER TOXICITY; LOW DRUG DOSE; MAXIMUM PLASMA CONCENTRATION; MENTAL DISEASE; NAUSEA; NEUROPATHIC PAIN; NONHUMAN; PAIN; PHARMACODYNAMICS; PHARMACOGENETICS; POSTOPERATIVE PAIN; PRESCRIPTION; QT PROLONGATION; RESPIRATION DEPRESSION; REVIEW; SEDATION; SIDE EFFECT; SINGLE DRUG DOSE; SOMNOLENCE; STOMACH DISEASE; STOMACH ULCER; UNSPECIFIED SIDE EFFECT; VISUAL DISORDER; DRUG DETOXIFICATION; GENETIC VARIABILITY; GENETICS; STANDARD;

ANALGESICS; CARRIER PROTEINS; CYTOCHROME P-450 ENZYME SYSTEM; HUMANS; METABOLIC DETOXICATION, DRUG; PHARMACOGENETICS; PRESCRIPTIONS, DRUG; VARIATION (GENETICS);

EID: 49949097665     PISSN: 14622416     EISSN: 17448042     Source Type: Journal    
DOI: 10.2217/14622416.9.7.905     Document Type: Review

References (265)

1. Sadee W, Dai Z: Pharmacogenetics/genomics and personalized medicine. Hum. Mol. Genet. 14, 207-214 (2005).
2. Flores CM, Mogil JS: The pharmacogenetics of analgesia: toward a genetically-based approach to pain management. Pharmacogenomics 2, 177-194 (2001).
3. Higgins CF: ABC, transporters: physiology, structure and mechanism - an overview. Res. Microbiol. 152, 205-210 (2001).
4. Schwab M, Eichelbaum M, Fromm MF: Genetic polymorphisms of the human MDR1 drug transporter. Annu. Rev. Pharmacol. Toxicol. 43, 285-307 (2003).
5. Wang JS, Newport DJ, Stowe ZN, Donovan JL, Pennell PB, DeVane CL: The emerging importance of transporter proteins in the psychopharmacological treatment of the pregnant patient. Drug Metab. Rev. 39, 723-746 (2007).
6. Hoffmeyer S, Burk O, von Richter O et al.: Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proc. Natl. Acad. Sci. USA 97, 3473-3478 (2000).
7. Marzolini C. Paus E, Bucan T, Kim RB: Polymorphisms in human MDR1 (P-glycoprotein): recent advances and clinical relevance. Clin. Pharmacol. Ther. 75, 13-33 (2004).
8. Hoffmeyer S, Burk O, von Richter O et al.: Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo Proc. Natl Acad. Sci USA 97, 3473-3478 (2000).
9. Johne A, Kopke K, Gerioff T et al.: Modulation of steady-state kinetics of digoxin by haplotypes of the P-glycoprotein MDR1 gene. Clin. Pharmacol. Ther. 72, 584-594 (2002).
10. Fellay J, Marzolini C, Meaden ER et al.: Response to antiretroviral treatment in HIV-1-infected individuals with allelic variants of the multidrug resistance transporter 1: a pharmacogenetics study. Lancet 359, 30-36 (2002).
11. Kerb R: Implications of genetic polymorphisms in drug transporters for pharmacotherapy. Cancer-Lett. 234, 4-33 (2006).
12. Sakaeda T: MDR1 genotype-related pharmacokinetcs: fact or fiction? Drug. Metab. Pharmacokinet. 20, 391-414 (2005).
13. Oude Elferink M, Zadim J: MDR1 P-glycoprotein transports endogenous opioid peptides. Peptides 22, 2015-2020 (2001).
14. Xie R, Hammarlund-Udenaes M, de Boer AG, de Lange EC: The role of P-glycoprotein in blood-brain barrier transport of morphine: transcortical microdialysis studies in MDR1A (-/-) and mdr1a (+/+) mice. Br. J. Pharmacol. 128, 563-568 (1999).
15. King M, Su W, Chang A, Zuckerman A, Pasternak GW: Transport of opioids from the brain to the periphery by P-glycoproteln: peripheral actions of central drugs. Nat. Neurosci. 4, 268-274 (2001).
16. Letrent SP. Pollack GM, Brouwer KR, Brouwer LR: Effect of GF 120918, a potent P-glycoprotein inhibitor, on morphine pharmacokinetics and pharmacodynamics in rat. Pharm. Res. 15, 599-605 (1998).
17. Kharasch ED, Hoffer C, Whittington D, Sheffels P: Role of P-glycoprotein absorption and clinical effects of morphine. Clin. Pharmacol. Ther. 74, 543-554 (2003).
18. Skarke C, Jarrar M, Erb K, Schmidt H, Geisslinger G, Lotsch J: Respiratory and miotic effects of morphine in healthy volunteers when P-glycoprotein is blocked by quinidine. Clin. Pharmacol. Ther. 74, 303-311 (2003).
19. Klepstad P, Dale O, Skorpen F, Borchgrevink PC, Kaasa S: Genetic variability and clinical efficacy of morphine. Acta Anaesthesiol. Scand. 49, 902-908 (2005).
20. Meineke I, Freudenthaler S, Hofmann U et al.: Pharmacokinetic modelling of morphine, morphine-3-glucurunide and morphine-6-glucuronide in plasma and cerebrospinal fluid of neurosurgical patients after short-term infusion of morphine. Br. J. Clin. Pharmacol. 54, 592-603 (2002).
21. Coulbault L, Beaussier M, Verstuyft C et al.: Environmental and genetic factors associated with morphine response in the postoperative period. Clin. Pharmacol. Ther. 79, 316-324 (2006).
22. Thompson SJ, Koszdin K, Bernards CM: Opiate induced analgesia is increased and prolonged in mice lacking P-glycoprotein. Anesthesiology 92, 1392-1399 (2000).
23. Wang JS, Ruan Y, Taylor RM, Donovan JL, Markowitz JS, DeVane CL: Brain penetration of methadone (R)- and (S)-enantiomers is greatly increased by P-glycoprotein deficiency in the blood-brain barrier of ABCB1A gene knockout mice. Psychopharmacology 173, 132-138 (2004).
24. Kharasch ED, Hoffer C, Whittington D: The effect of quinidine, used as a probe for the involvement of P-glycoprotein, on the intestinal absorption and pharmacodynamics of methadone. Br. J. Clin. Pharmacol. 57, 600-610 (2003).
25. Lötsch J, Skarke C, Wieting J et al.: Modulation of the central nervous effects of levomethadone by genetic polymorphisms potentially affecting its metabolism, distribution, and drug action. Clin. Pharmacol. Ther. 76, 72-89 (2006).
26. Crettol S, Déglon JJ, Besson J et al.: ABCB1 and cytochrome P450 genotypes and phenotypes: Influence on methadone plasma levels and response to treatment. Clin. Pharmacol. Ther. 80, 668-681 (2006).
27. Coller JK, Barrat DT, Dahlen K, Loennechen MH, Somogyi AA: ABCB1 genetic variability and methadone dosage requirement in opioid-dependent individuals. Clin. Pharmacol. Ther. 80, 683-690 (2006).
28. Crettol S, Déglon JJ, Besson J et al.: No influence of ABCB1 haplotypes on methadone dosage requirement. Clin. Pharmacol Ther. 83, 668-669 (2008).
29. Henthorn TK, Liu Y, Mahapatro M, Ng KY: Active transport of fentanyl by the blood-brain barrier. J. Pharmacol. Exp. Ther. 289, 1084-1089 (1999).
30. Cirella VN, Pantuck CB, Lee YJ. Pantick EJ: Effects of cyclosporine on anesthetic action. Anesth. Analg. 66, 703-706 (1987).
31. Kharasch ED, Hoffer C, Altuntas TG, Whittington D: Quinidine as a probe for the role of P-glycoprotein in the intestinal absorption and clinical effects of fentanyl. J. Clin. Pharmacol. 44, 224-233 (2004).
32. Park HJ, Shinn HK, Ryu SH, Lee HS, Park CS, Kang JH: Genetic polymorphisms in the ABCB1 gene and the effects of fentanyl in Koreans. Clin. Pharmacol. Ther. 81, 539-546 (2007).
33. Kalvass JC, Maurer TS, Pollack GM: Use of plasma and brain unbound fractions to assess the extent of brain distribution of 34 drugs: comparison of unbound concentration ratios to in vivo P-glycoprotein efflux ratios. Drug Metab. Dispos. 35, 660-666 (2007).
34. Waters CM, Avram MJ, Krejcie TC, Henthorn TK: Uptake of fentanyl in pulmonary endothelium. J. Pharmacol. Exp. Ther. 288, 157-163 (1999).
35. Wandel C, Kim R, Wood M, Wood A: Interaction of morphine, fentanyl, sufentanil, alfentanil, and loperamide with the efflux drug transporter P-glycoprotein. Anesthesiology 96, 913-920 (2002).
36. Kalvass JC, Olson ER, Pollack GM: Pharmacokinetics and pharmacodynamics of alfentanil in P-glycoprotein-competent and P-glycoprotein-deficient mice: P-glycoprotein efflux alters alfentanil brain disposition and antinociception. Drug. Metab. Dispos. 35, 455-459 (2007).
37. Callaghan R, Riordan JR: Synthetic and natural opiates interact with P-glycoprotein in multidrug-resistant cells. J. Biol. Chem. 268, 16059-16064 (1993).
38. Desmeules JA, Piguet V, Ehret GB, Dayer P. Pharmacogenetics, pharmacokinetics, and analgesia. In: The Genetics of Pain, Progress in Pain Research and Management. Mogil JS (Ed.). IASP Press, WA, USA, 211-238 (2004).
39. Boström E, Simonsson US, Hammarlund-Udenaes M: Oxycodone pharmacokinetics and pharmacodynamics in the rat in the presence of the P-glycoprotein inhibitor PSC833. J. Pharm. Sci. 94, 1060-1066 (2005).
40. Hassan HE, Myers AL, Lee IJ, Coop A, Eddington ND: Oxycodone induces overexpression of P-glycoprotein (ABCB1) and affects paclitaxel's tissue distribution in Sprague Dawley rats. J. Pharm. Sci. 96, 2494-2506 (2007).
41. Sadeque AJ, Wandel C, He H, Shah S, Wood AJ: Increased drug delivery to the brain by P-glycoprotein inhibition. Clin. Pharmacol. Ther. 68, 231-237 (2000).
42. Skarke C, Jarrar M. Schmidt H et al.: Effects of ABCB1 (multidrug resistance transporter) gene mutations on disposition and central nervous effects of loperamide in healthy volunteers. Pharmacogenetics 13, 651-660 (2003).
43. Slanar O, Nobilis M, Kvetina J, Matouskova O, Idle JR, Perlik F: Pharmacokinetics of tramadol is affected by MDR1 polymorphism C3435T Eur. J. Clin. Pharmacol. 63. 419-421 (2007).
44. Kanaan M, Daali Y, Dayer P. Desmeules J: Lack of interaction of the NMDA receptor antagonists dextromethorphan and dextrorphan with P-glycoprotein. Curr. Drug Metab. 9(2), 144-151 (2008).
45. Buclin T, Biollaz J, Diézi J: Transports rénaux de médicaments: mécanismes et potentiel d'interactions. Med. Hyg. 62, 682-692 (2004).
46. Awara WM, El-Sisi AE, El-Sayad ME, Goda AE: The potential role of cyclooxygenase-2 inhibitors in the treatment of experimentally-induced mammary tumour: does celecoxib enhance the anti-tumour activity of doxorubicin? Pharmacol. Res. 50, 487-498 (2004).
47. Perloff MD, Störmer E, von Moltke LL, Greenblatt DJ: Rapid assessment of P-glycoprotein inhibition and induction in vitro. Pharm. Res. 20, 1177-1183 (2003).
48. Flescher E, Rotem R, Kwon P, Azare J, Jaspers I, Cohen D: Aspirin enhances multidrug resistance gene 1 expression in human Molt-4 T lymphoma cells. Anticancer Res. 20, 4441-4444 (2000).
49. Lu AY, West SB: Multiplicity of mammalian microsomal cytochromes P-450. Pharmacol. Rev. 31, 277-295 (1979).
50. Shimada T, Yamazaki H, Mimura M, Inui Y, Guengerich FP: 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 (1994).
51. Donato MT, Castell JV: Strategies and molecular probes to investigate the role of cytochrome P450 in drug metabolism: focus on in vitro studies. Clin. Pharmacokinet. 42, 153-178 (2003).
52. Zhou H, Josephy D, Kim D, Guengerich P: Functional characterization of four allelic variants of human cytochrome P450 1A2, Arch. Biochem. Biophys. 422, 23-30 (2004).
53. Ingelman-Sundberg M, Sim SC, Gomez A, Rodriguez-Antona C: Influence of cytochrome P450 polymorphisms on drug therapies: pharmacogenetic, pharmacoepigenetic and clinical aspects. Pharmacol. Ther. 116, 496-526 (2007).
54. Moody DE, Alburges ME, Parker RJ, Collins JM, Strong JM: The involvement of cytochrome P450 3A4 in the N-demethylation of L-α-acetylmethadol (LAAM), norLAAM, and methadone. Drug. Metab. Dispos. 25, 1347-1353 (1997).
55. Herrlin K, Segerdahl M, Gustafsson LL, Kalso E: Methadone, ciprofloxacin, and adverse drug reactions. Lancet. 356, 2069-2070 (2000).
56. Miners JO, Coulter S, Tukey RH, Veronese ME, Birkett DJ: Cytochromes P450, 1A2, and 2C9 are responsible for the human hepatic O-demethylation of R- and S-naproxen. Biochem. Pharmacol. 26, 1003-1008 (1996).
57. Raucy JL, Lasker JM, Liebler CS, Black M: Acetaminophen activation by human liver cytochromes P4502E1 and P4501A2. Arch. Biochem. Biophys. 271, 270-283 (1989).
58. Zanger UM, Klein K, Saussele T, Blievernicht J. Hofmann MH, Schwab M: Polymorphic CYP2B6: molecular mechanisms and emerging clinical significance. Pharmacogenomics, 743-759 (2007).
59. Kharasch ED, Hoffer C, Whittington D, Sheffels P: Role of hepatic and intestinal cytochrome P450 3A and 2B6 in the metabolism, disposition, and mitotic effects of methadone. Clin. Pharmacol. Ther. 76, 250-269 (2004).
60. Crettol S, Déglon JJ. Besson J et al.: Methadone enantiomer plasma levels, CYP2B6, 2C19, and 2C9 genotypes, and response to treatment. Clin. Pharmacol. Ther. 78, 593-604 (2005).
61. Eap CB, Crettol S, Rougier JS et al.: Stereoselective block of hERG channel by (S)-methadone and QT interval prolongation on CYP2B6 slow metababolizers. Clin. Pharmacol. Ther. 81, 719-728 (2007).
62. Zhang W, Ramamoorthy Y, Tyndale RF, Sellers EM: Interaction of buprenorphine and its metabolite norbuprenorphine with cytochromes P450 in vitro. Drug Metab. Dispos. 31, 768-772 (2003).
63. Umehara K, Shimokama Y, Miyamoto G: Inhibition of human drug metabolizing cytochrome P450 by buprenorphine. Biol. Pharm. Bull. 25, 682-685 (2002).
64. Subrahmanyam V, Renwick AB, Walters DG et al.: Identification of cytochrome P-450 isoforms responsible for cis-tramadol metabolism in liver microsomes. Drug Metab. Dispos. 29, 1146-1155 (2001).
65. Ramirez J, Innocenti F, Schuetz EG et al.: CYP2B6, CYP3A4, and CYP2C19 are responsible for the in vitro N-demethylation of meperidine in human liver microsomes. Drug Metab. Dispos. 32, 930-936 (2004).
66. Bort R, Mace K, Boobis A, Gomez-Lechon MJ, Pfeifer A, Castell J: Hepatic metabolism of diclofenac: role of human CYP in the minor oxidative pathways. Biochem. Pharmacol. 58, 787-796 (1999).
67. Saussele T, Burk O, Blievernicht JK et al.: Selective induction of human hepatic cytochromes P450 2B6 and 3A4 by metamizole. Clin. Pharmacol. Ther. 82, 265-274 (2007).
68. Kirchheiner J, Brockmöller J: Clinical consequences of cytochrome P450 2C9 polymorphisms. Clin. Pharmacol. Ther. 77, 1-16 (2005).
69. Lee CR, Goldstein JA, Pieper JA: Cytochrome P450 2C9 polymorphisms: a comprehensive review of the in vitro and human data. Pharmacogenetics 12, 251-263 (2002).
70. Totah RA, Rettie AE: Cytochrome P450 2C8: substrates, inhibitors, pharmacogenetics and clinical relevance. Clin. Pharmacol. Ther. 77, 341-352 (2005).
71. Yasar U, Lundgren S, Eliasson E et al.: Linkage between the CYP2C8 and CYP2C9 genetic polymorphisms. Biochem. Biophys. Res. Commun. 299, 25-28 (2002).
72. Leemann TD, Transon C, Bonnabry P, Dayer P: A major role for cytochrome P450TB (CYP2C subfamily) in the actions of non-steroidal antiinflammatory drugs. Drugs Exp. Clin. Res. 19, 189-195 (1993).
73. Martinez C, Blanco G, Ladero JM et al. Genetic predisposition to acute gastrointestinal bleeding after NSAIDs use. Br. J. Clin. Pharmacol. 141, 205-208 (2004).
74. Pilotto A, Seripa D, Franceschi M et al.: Genetic susceptibility to nonsteroidal anti-inflammatory drug-related gastroduodenal bleeding: role of cytochrome P450 2C9 polymorphisms. Gastroenterology 133, 465-471 (2007).
75. Martin JH, Begg EJ, Kennedy MA, Roberts R, Barclay ML: Is cytochrome P450 2C9 genotype associated with NSAID gastric ulceration? Br. J. Clin. Pharmacol. 51, 627-630 (2001).
76. Vonkeman HE, van de Laar MA, van der Palen J, Brouwers JR, Vermes I: Allele variants of the cytochrome P450 2C9 genotype in white subjects from The Netherlands with serious gastroduodenal ulcers attributable to the use of NSAIDs. Clin. Ther. 28, 1670-1676 (2006).
77. Dorado P, Berecz R, Norberto MJ, Yasar U, Dahl ML, Llerena A: CYP2C9 genotypes and diclofenac metabolism in Spanish healthy volunteers. Eur. J. Clin. Pharmacol. 59, 221-225 (2003).
78. Brenner SS, Herrlinger C, Dilger K et al.: Influence of age and cytochrome P450 2C9 genotype on the steady-state disposition of diclofenac and celecoxib. Clin. Pharmacokinet. 42, 283-292 (2003).
79. Kirchheiner J, Meineke I, Steinbach N, Meisel C, Roots I, Brockmoller J: Pharmacokinetics of diclofenac and inhibition of cyclooxygenases 1 and 2: no relationship to the CYP2C9 genetic polymorphism in humans. Br. J. Clin. Pharmacol. 55, 51-61 (2003).
80. Aithal GP, Day CP, Leathart JBS, Daly AK: Relationship of polymorphism in CYP2C9 to genetic susceptibility to diclofenac-induced hepatitis. Pharmacogenetics 10, 511-518 (2000).
81. Garcia-Martin E, Martinez C, Tabares B, Frias J, Agundez JAG: Interindividual variability in ibuprofen pharmacokinetics is related to interaction of cytochrome P450 2C8 and 2C9 amino acid polymorphisms. Clin. Pharmacol. Ther. 76, 119-127 (2004).
82. Hamman MA, Thompson GA, Hall SD: Regioselective and stereoselective metabolism of ibuprofen by human cytochrome P450 2C. Biochem. Pharmacol. 54, 33-41 (1997).
83. Kirchheiner J, Meineke I, Freytag G, Meisel C, Roots I, Brockmoller J: Enantiospecific effects of cytochrome P450 2C9 amino acid variants on ibuprofen pharmacokinetics and on the inhibition of cyclooxygenases 1 and 2. Clin. Pharmacol. Ther. 72, 62-75 (2002).
84. Lee CR, Pieper JA, Frye RF, Hinderliter AL, Blaisdell JA, Goldstein JA: Differences in flurbiprofen pharmacokinetics between CYT2C9*1/ *1, *1/*2 and *1/*3 genotypes. Eur. J. Clin. Pharmacol. 58, 791-794 (2003).
85. Lundblad MS, Ohlsson S, Johansson P, Lafolie P, Eliasson E: Accumulation of celecoxib with a 7 -fold higher drug exposure in individuals homozygous for CYP2C9*3. Clin. Pharmacol. Ther. 79, 287-288 (2006).
86. Tang C, Shou M, Mei Q, Rushmore TH. Rodrigues AD: Major role of human liver microsomal cytochrome P450 2C9 in the oxidative metabolism of celecoxib a novel cyclooxygenase II inhibitor. J. Pharmacol. Exp. Ther. 293, 453-459 (2000).
87. Tang C, Shou M, Rushmore TH et al.: In vitro metabolism in celecoxib, cyclooxygenase 2 inhibitor by allelic variant forms of human liver microsomal cytochrome P450 C9: correlation with CYPC9 genotype and in vivo pharmacokinetics. Pharmacogenetics 11, 223-235 (2001).
88. Kirchheiner J, Störmer E, Meisel C, Steinbach N, Roots I, Brockmoller J: Influence of CYP2C9 genetic polymorphisms on pharmacokinetics of celecoxib and its metabolites. Pharmacogenetics 13, 473-480 (2003).
89. Zhao J, Leemann T, Dayer P: In vitro oxidation of oxicam NSAIDS by a human liver cytochrome P450. Life Sci. 51. 575-581 (1992).
90. Takanashi K, Tainaka H, Kobayashi K, Yasumori T: Hosakawa M, Chiba K: CYP2C9 Ile359 and Leu359 variants: enzyme kinetic study with seven substrates. Pharmacogenetics 10, 95-104 (2000).
91. Lida I, Miyata A, Arai M et al.: Catalytic roles of CYP2C9 and its variants (CYP2C9*2 and CYP2C9*3) in lornoxicam 5 -hydroxylation. Drug. Metab. Dispos. 32, 7-9 (2004).
92. Gun Y, Zhang Y, Wang Y et al.: Role of CYP2C9 and its variants ( CYP2C9*3 and CYP2C9*13) in the metabolism of lornoxicam in human. Drug. Metab. Dispos. 33, 749-753 (2005).
93. Vianne-Jorge R, Perini JA, Rondinelli E, Suarez-Kurtz G: CYP2C9 genortypes and the pharmacokinetics of tenoxicam in Brazilians. Clin. Pharmacol. Ther. 76, 18-26 (2004).
94. Perini JA, Vianne-Jorge R, Brogliato AR, Suarez-Kurtz G: Influence of CYP2C9 genotypes on the pharmacokinetics and pharmacodynamics of piroxicam. Clin. Pharmacol. Ther. 78, 362-369 (2005).
95. Bigler J, Whitton J, Lampe JW, Fosdick L, Bostick RM. Potter JD: CYP2C9 and UGT1A6 genotypes modulate the protective effects of acetylsalicylic acid on colon adenoma risk. Cancer Res. 61, 3566-3569 (2001).
96. Samowitz WS, Wolff RK, Curtin K et al.: Interactions between CYP2C9 and UGT1A6 polymorphisms and nonsteroidal anti-inflammatory drugs in colorectal cancer prevention. Clin. Gastroenterol. Hepatol. 4, 894-901 (2006).
97. van Oijen MGH, Huybers S, Peters WHM et al.: Polymorphisms in genes encoding acetylsalicylic acid metabolizing enzymes are unrelated to upper gastrointestinal health in cardiovascular patients on acetylsalicylic acid. Br. J. Clin. Pharmacol. 60, 623-628 (2005).
98. Levy RH: Cytochrome P450 isozymes and antiepileptic drug interactions. Epilepsia 36 (Suppl. 5), S8-S13 (1995).
99. Desta Z, Zhao X Shin JG, Flockhart D: Clinical significance of the cytochrome 450 2C19 genetic polymorphisms. Clin. Pharmacokinet. 41, 913-958 (2002).
100. Sim SC, Risinger C, Dahl ML et al.: A common novel CYP2C19 gene variant causes ultrarapid drug metabolism relevant for the drug response to proton pump inhibitors and antidepressants. Clin. Pharmacol. Ther. 79, 103-113 (2006).
101. Gerber JG. Rhodes RJ, Gal J: Sterebselective metabolism of methadone N-demethylation by cytochrome P4502B6 and 2C19. Chirality 16, 36-44 (2004).
102. McGinnity DF, Parker AJ. Soars M, Riley RJ: Automated definition of the enzymology of drug oxidation by the major human drug metabolizing cytochrome P450s. Drug Metab. Dispos. 28, 1327-1334 (2000).
103. Chen XP, Tan ZR, Huang SL, Huang Z, Ou-Yang DS, Zhou HH: Isozyme-specific induction of low-dose aspirin on cytochrome P450 in healthy subjects. Clin. Pharmacol. Ther. 73, 264-271 (2003).
104. Zanger UM, Raimondo S, Eichelbaum M: Cytochrome P450 2D6: overview and update on pharmacology, genetics, biochemistry. Naunyn Schmiedebergs Arch. Pharmacol. 369, 23-37 (2004).
105. Cascorbi I: Pharmacogenetics of cytochrome 2D6: genetic background and clinical implication. Eur. J. Clin. Investig. 33, 17-22 (2003).
106. Sistonen J, Sajantila A, Lao O, Corander J, Barbujani G, Fuselli S: CYP2D6 worldwide genetic variation shows high frequency of altered activity variants and no continental structure. Pharmacogenet. Genomics 17, 93-101 (2007).
107. Dayer P, Desmeules J, Leemann T, Striberni R: Bioactivation of the narcotic drug codeine in human liver is mediated by the polymorphic monooxygenase catalyzing debrisoquine 4-hydroxylation (cytochrome P450 dbl/bufI). Biochem. Biophys. Res. Commun. 152, 411-416 (1988).
108. Yue QY, Hasselstrom J, Svensson JO, Sawe J: Pharmacokinetics of codeine and its metabolites in Caucasian healthy volunteers: comparisons between extensive and poor hydroxylators of debrisoquine. Br. J. Clin. Pharmacol. 31, 635-642 (1991).
109. Chen ZR, Somogyi AA, Reynolds G, Bochner F: Disposition and metabolism of codeine after single and chronic doses in one poor and seven extensive metabolisers. Br. J. Clin. Pharmacol. 31, 381-390 (1991).
110. Desmeules J, Gascon MP, Dayer P, Magistris M: Impact of environmental and genetic factor on codeine analgesia. Eur. J. Clin. Pharmacol. 41, 23-26 (1991).
111. Poulsen L, Brosen K, Arendt-Nielsen L, Gram LF, Elbaek K, Sindrup SH: Codeine and morphine in extensive and poor metabolizers of sparteine: pharmacokinetics, analgesic effect and side effects. Eur. J. Clin. Pharmacol. 51, 289-295 (1996).
112. Caraco Y, Sheller J, Wood AJJ: Pharmacogenetic determination of the effects of codeine and prediction of drug interactions. J. Pharm. Exp. Ther. 278, 1165-1174 (1996).
113. Caraco Y, Sheller J, Wood AJJ: Impact of ethnic origin and quinidine coadministration on codeine's disposition and pharmacodynamic effects. J. Pharmacol. Exp. Ther. 290, 413-422 (1999).
114. Lötsch J, Skarke C, Schmidt H et al.: Evidence for morphine-independent central nervous opioid effects after administration of codeine: contribution of other codeine metabolites. Clin. Pharmacol. Ther. 79, 35-48 (2006).
115. Kirchheiner J, Schmidt H, Tzvetkov M et al.: Pharmacokinetics of codeine and its metabolite morphine in ultra-rapid metabolizers due to CYP2D6 duplication. Pharmacogenomics J. 7, 257-265 (2007).
116. Dalen P, Frengell C, Dahl ML, Sjoqvist F: Quick onset of severe abdominal pain after codeine in an ultrarapid metabolizer of debrisoquine. Ther. Drug Monit. 19, 543-544 (1997).
117. Gasche Y, Daali Y, Fathi M et al.: Codeine intoxication associated with ultrarapid CYP2D6 metabolism. N. Engl. J. Med. 351, 2827-2831 (2004).
118. Koren G, Cairns J, Chitayat A, Leeder SJ: Pharmacogenetics of morphine poisoning in a breastfed neonate of a codeine-prescribed mother. Lancet 368, 704 (2006).
119. Paar WD, Poche S, Gerloff J, Dengler HJ: Polymorphic CYP2D6 mediates O-demethylation of the opioids analgesic tramadol. Eur. J Clin. Pharmacol. 53, 235-239 (1997).
120. Collart L, Luthy C, Favario-Constantin C, Dayer P: Duality of the analgesic effect of tramadol in humans. Schweiz Med Wochenschr. 123, 2241-2243 (1993).
121. Poulsen L, Arendt-Nielsen L, Brosen K, Sindrup SH: The hypoalgesic effect of tramadol relation to CYP2D6. Clin. Pharmacol. Ther. 60, 636-644 (1996).
122. Stamer UM, Lehnen K, Hothker F et al.: Impact of CYP2D6 on postoperative tramadol analgesia. Pain 105, 231-238 (2003).
123. Desmeules JA, Piguet V, Collart L, Dayer P: Contribution of monoaminergic modulation to the analgesic effect of tramadol. Br. J. Clin. Pharmacol. 41, 7-12 (1996).
124. Stamer UM, Musshoff F, Kobilay M, Madea B, Hoeft A, Stuber F: Concentrations of tramadol and O-desmethyltramadol enantiomers in different CYP2D6 genotypes. Clin. Pharmacol. Ther. 82, 41-47 (2007).
125. Wang G. Zhang H, He F, Fang X: Effect of the CYP2D6*10 C188T polymorphism on postoperative tramadol analgesia in a Chinese population. Eur. J. Clin. Pharmacol. 62, 927-931 (2006).
126. Kirchheiner J, Keulen JT, Bauer S, Roots I, Brockmöller J: Effects of the CYP2D6 gene duplication on the pharmacokinetics and pharmacodynamics of tramadol. J. Clin. Psychopharmacol. 28, 78-83 (2008).
127. Kirkwood LC, Nation RL, Somogyi AA: Characterization of the human cytochrome P450 enzymes involved in the metabolism of dihydrocodeine. Br. J. Clin. Pharmacol. 44, 549-555 (1997).
128. Hutchinson MR, Menelaou A, Foster DJ, Colter JK, Somogyi AA: CYP2D6 and CYP3A4 involvement in the primary oxidative metabolism of hydrocodone by human liver microsomes. Br. J. Clin. Pharmacol. 57, 287-297 (2004).
129. Lalovic B, Kharash E, Hoffer C, Risler L, Liu-Chen LY, Shen DD: Pharmacokinetic and pharmacodynamics of oral oxycodone in healthy human subjects: role of circulating active metabolites. Clin. Pharmacol. Ther. 79, 461-479 (2006).
130. Schmidt H, Vormfelde SV, Walchner-Bonjean M et al.: The role of active metabolites in dihydrocodeine effects. Int. J. Clin. Pharmacol. Ther. 41, 95-106 (2003).
131. Wilder-Smith CH, Hufschmid E, Thormann W: The visceral and somatic antinociceptive effects of dihydrocodeine and its metabolite, dihydromorphine. A cross-over study with extensive and quinidine-induced poor metabolizers. Br. J. Clin. Pharmacol. 45, 575-581 (1998).
132. Webb JA, Rostmi-Hodjegn A, Abdul-Manap, R, Hofmann U, Mikus G, Kamali G: Contribution of dihydrocodeine and dihydromorphine to analgesia following dihydrocodeine administration in a man: a PK-PD modeling analysis. Br. J. Clin. Pharmacol. 52, 35-43 (2001).
133. Otton SV, Schadel M, Cheung SW, Kaplan HL, Busto UE, Sellers EM: CYP2D6 phenotype determines the metabolic conversion of hydrocodone to hydromorphone. Clin. Pharmacol. Ther. 54, 463-472 (1993).
134. Kaplan HL, Busto UE, Baylon GJ et al.: Inhibition of cytochrome P450 2D6 metabolism of hydrocodone to hydromorphone does not importantly affect abuse liability. J. Pharmacol. Exp. Ther. 281, 103-108 (1997).
135. Maddocks I, Sommogyi A, Abbott F, Hayball P. Parker D: Attenuation of morphine-induced delirium in palliative care by substitution with infusion of oxycodone. J. Pain Symptom. Manage. 12, 182-189 (1996).
136. Myers AB, Sullivan JE, Koller DM et al.: Correlation of CYP2D6 genotype with response to oxycodone in orthopedic injury related pain. Clin. Pharmacol. Ther. 79, P18 (2005).
137. Susce MT, Murray-Carmichael E, de Leon J: Response to hydrocodone, codeine and oxycodone in a CYP2D6 poor metabolizer. Prog. Neuropsychopharmacol Biol. Psychiatry 30, 1356-1358 (2006).
138. de Leon J, Dinsmore L. Wedlund P: Adverse drug reactions to oxycodone and hydrocodone in CYP2D6 ultrarapid metabolizers. J. Clin. Psychopharmacol. 23, 420-421 (2003).
139. Samer C, Daah Y, Rebsamen M, Chiappe A, Desmeules J, Dayer P: Determinant role of CYP2D6 and CYP3A4 pathways on the antinociceptive effects of oxycodone. Clin. Pharmacol. Ther. 79, P57 (2006).
140. Eap CB, Broly F, Baumann P: Cytochrome P450 2D6 genotype and methadone steady-state concentrations. J. Clin. Psychopharmacol. 21, 229-234 (2001).
141. Uehlinger C, Crettol S, Chassot P et al.: Increased (R)-methadone plasma concentrations by quetiapine in cytochrome P450s and ABCB1 genotyped patients. J. Clin. Psychopharmacol. 27, 273-278 (2007).
142. Pérez de los Cobos J, Siñol N, Trujols J et al.: Association of CYP2D6 ultrarapid metabolizer genotype with deficient patient satisfaction regarding methadone maintenance treatment. Drug Alcohol Depend. 89, 190-194 (2007).
143. Coller JK, Joergensen C, Foster DJ et al.: Lack of influence of CYP2D6 genotype on the clearance of (R)-, (S)- and racemic-methadone. Int. J. Clin. Pharmacol. Ther. 45, 410-417 (2007).
144. Wu D, Otton SV, Sproule BA et al.: Inhibition of human cytochrome P450 2D6 (CYP2D6) by methadone. Br. J. Clin. Pharmacol. 35, 30-34 (1993).
145. Shiran MR, Chowdry J, Rostami-Hodjegan A et al.: A discordance between cytochrome P450 2D6 genotype and phenotype in patients undergoing methadone maintenance treatment. Br. J. Clin. Pharmacol. 56, 220-224 (2003).
146. Zhu W, Cadet P, Baggerman G, Mantione KJ, Stefano GB: Human white blood cells synthesize morphine: CYP2D6 modulation. J. Immunol. 175, 7357-7362 (2005).
147. Candiotti KA, Yang Z, Curia L et al.: The impact of CYP2D6 genetic polymorphism on postoperative morphine consumption. Abstracts of the 2008 Annual Meeting of the American Academy of Pain Medicine. February 12-16, Orlando, FL, USA, (2008).
148. Desmeules JA, Kondo Oestreicher M, Piguet V, Allaz AF, Dayer P: Contribution of cytochrome P4502D6 phenotype to the neuromodulatory effects of dextromethorphan. J. Pharmacol. Exp. Ther. 288, 607-612 (1999).
149. Dayer P, Leemann T, Stirberni R: Dextromethorphan O-demethylation in liver microsomes as a prototype reaction to monitor cytochrome P450 db1 activity. Clin. Pharmacol. Ther. 45, 34-40 (1989).
150. Carpenter CL, Marks SS, Watson DL, Greenberg DA: Brain dextromethorphan and dextrorphan as calcium channel antagonists. Brain Res. 439, 372-375 (1988).
151. Wong BY, Coulter DA, Choi DW, Prince DA: Dextrorphan and dextromethorphan, common antitussives, are antiepileptic and antagonize N-methyl-D-aspartate in brain slices. Neurosci. Lett. 85, 261-266 (1988).
152. Steinberg GK, Bell TE, Yenari MA: Dose escalation safety and tolerance study of the N-methyl-D-aspartate antagonist dextromethorphan in neurosurgery patients. J. Neurosurg. 84, 860-866 (1996).
153. Desmeules JA, Kondo Oestreicher M, Piguet V, Allaz AF, Dayer P: Contribution of cytochrome P450 2D6 phenotype to the neuromodulatory effects of dextromethorphan. J. Pharm. Exp. Ther. 288, 607-612 (1999).
154. Pope LE, Khalil MH, Berg JE, Stiles M, Yakatan GJ, Sellers EM: Pharmacokinetics of dextromethorphan after single or multiple dosing in combination with quinidine in extensive and poor metabolizers. J. Clin. Pharmacol. 44, 1132-1142 (2004).
155. Ehret G, Chabert J, Daali Y et al.: Preemptive analgesia induced by the NMDA receptor antagonist dextromethorphan: a randomized controlled study evaluating the impact of CYP2D6 phenotype on the post-operative analgesic requirement of patient. 11th World Congress on Pain, IASP August 21-26, Sydney, Australia (2005).
156. Dong H, Haining RL, Thummel KE, Rettie AE, Nelson SD: Involvement of human cytochrome P450 2D6 in the bioactivation of acetaminophen. Drug Metab. Dispos. 28, 1397-1400 (2000).
157. Garnett WR: Clinical implications of drug interactions with coxibs. Pharmacotherapy 21, 1223-1232 (2001).
158. Ueshima Y, Tsutsumi M, Takase S, Matsuda Y, Kawahara H: Acetaminophen metabolism in patients with different cytochrome P-4502E1 genotypes. Alcohol Clin. Exp. Res. 20(Suppl. 1), 25A-28A (1996).
159. Lee SS, Buters JT, Pineau T, Fernandez-Salguero, P, Gonzalez FJ: Role of CYP2E1 in the hepatotoxicity of acetaminophen. J. Biol. Chem. 271, 12063-12067 (1996).
160. Ingelman-Sundberg M: Human drug metabolising cytochrome P450 enzymes: properties and polymorphisms. Naunyn Schmiedebergs Arch. Pharmacol. 369, 89-104 (2004).
161. Daly AK: Significance of the minor cytochrome P450 3A isoforms. Clin. Pharmacokinet. 45, 13-31 (2006).
162. Gonzalez FJ, Skoda RC, Kimura S et al.: Characterization of the common genetic defect in humans deficient in debrisoquine metabolism. Nature 331, 442-446 (1988).
163. Schirmer M, Rosenberg A, Klein K et al.: Sex-dependent genetic markers of CYP3A4 expression and activity in human liver microsomes. Pharmacogenomics 8, 443-453 (2007).
164. Lamba JK, Lin YS, Schuetz EG, Thummel KE: Genetic contribution to variable human CYP3A-mediated metabolism. Adv. Drug. Deliv. Rev. 54, 1271-1294 (2002).
165. Williams DG, Patel A, Howard RF: Pharmacogenetics of codeine metabolism in an urban population of children and its implications for analgesic reliability. Br. J. Anaesth. 89, 839-845 (2002).
166. Hustert E, Haberl M, Burk O et al.: The genetic determinants of the CYP3A5 polymorphism. Pharmacogenetics 11, 773-779 (2001).
167. Pinto AG, Wang YH, Chalasani N et al.: Inhibition of human intestinal wall metabolism by macrolide antibiotics: effect of clarithromycin on cytochrome P450 3A4/5 activity and expression. Clin. Pharmacol. Ther. 77, 178-188 (2005).
168. Tang W, Stearns RA, Wang RW, Chiu SHL, Baillie TA: Roles of human hepatic cytochrome P450s 2C9 and 3A4 in the metabolic activation of diclofenac. Chem. Res. Toxicol. 12, 192-199 (1999).
169. Rodrigues AD, Yang Z, Chen C, Pray D, Kim S, Sinz M: Is celecoxib an inducer of cytochrome P450 3A4 in subjects carrying the CYP2C9*3 allele? Clin. Pharmacol. Ther. 80, 298-301 (2006).
170. Rodrigues AD: Impact of CYP2C9 genotype on pharmacokinetics: are all cyclooxygenase inhibitors the same? Drug. Metab. Dispos. 33, 1567-1575 (2005).
171. Manyike PT, Kharasch ED, Kalhorn TF, Slattery JT: Contribution of CYP2E1 and CYP3A to acetaminophen reactive metabolite formation. Clin. Pharmacol. Ther. 67, 275-282 (2000).
172. Samer CF, Piguet V, Dayer P, Desmeules JA: Polymorphisme génétique et interactions médicamenteuses: leur importance dans le traitement de la douleur. Can. J. Anaesth. 52, 806-821 (2005).
173. Eap CB, Buclin T, Baumann P: Interindividual variability of the clinical pharmacokinetics of methadone: implications for the treatment of opioid dependence. Clin. Pharmacokinet. 41, 1153-1193 (2002).
174. Ehret GB, Desmeules J, Broers B: Methadone-associated long QT syndrome: improving pharmacotherapy for dependence on illegal opioids and lessons learned for pharmacology. Expert Opin. Drug Saf. 6, 289-303 (2007).
175. Niemi M, Backman JT, Fromm MF, Neuvonen PJ, Kivisto KT: Pharmacokinetic interactions with rifampicin: clinical relevance. Clin. Pharmacokinet. 42, 819-850 (2003).
176. Kharasch ED, Russel M, Mautz D et al.: The role of cytochrome P4503A4 in alfentanil clearance. Implications for interindividual variability in disposition and perioperative drug interactions. Anesthesiology 87, 36-50 (1997).
177. Bartkowski RR, Goldberg ME, Larijani GE, Boerner T: Inhibition of alfentanil metabolism by erythromycin. Clin. Pharmacol. Ther. 46, 99-102 (1989).
178. Palkama VJ, Neuvonen PJ, Olkkola KT: The CYP 3A4 inhibitor itraconazole has no effect on the pharmacokinetics of i.v. fentanyl. Br. J. Anaesth. 81, 598-600 (1998).
179. Olkkola KT, Palkama VJ, Neuvonen PJ: Ritonavir's role in reducing fentanyl clearance and prolonging its half-life. Anesthesiology 3, 681-685 (1999).
180. Hallberg P, Marten L, Wadelius M: Possible fluconazole-fentanyl interaction - a case report. Eur. J. Clin. Pharmacol. 62, 491-492 (2006).
181. Guitton J, Buronfosse T, Désage M, Lepape A, Brazier JL, Beaune P: Possible involvement of multiple cytochrome P450S in fentanyl and sufentanil metabolism as opposed to alfentanil. Biochem. Pharmacol. 53, 1613-1619 (1997).
182. Tateishi T, Krivoruk Y, Ueng YF, Wood AJ, Guengerich FP, Wood M: Identification of human liver cytochrome P-450 3A4 as the enzyme responsible for fentanyl and sufentanil N-dealkylation. Anesth. Analg. 82, 167-172 (1996).
183. Bartkowski RR, Goldberg ME, Huffnagle S, Epstein RH: Sufentanil disposition. Is it affected by erythromycin administration? Anesthesiology 78, 260-265 (1993).
184. Mackenzie PI, Owens IS, Burchell B et al.: The UDP glycosyltransferase gene superfamily: recommended nomenclature update based on evolutionary divergence. Pharmacogenetics 7, 255-269 (1997).
185. Mano Y, Usui T, Kamimura H: Predominant contribution of UDP-glucuronosyltransferase 2B7 in the glucuronidation of racemic flurbiprofen in the human liver. Drug. Metab. Dispos. 35, 1182-1187 (2007).
186. Tang W: The metabolism of diclofenac - enzymology and toxicology perspectives. Curr. Drug. Metab. 4, 319-329 (2003).
187. Mano Y, Usui T, Kamimura H: Contribution of UDP-glucuronosyltransferases 1A9 and 2B7 to the glucuronidation of indomethacin in the human liver. Eur. J. Clin. Pharmacol. 63, 289-296 (2007).
188. Mano Y, Usui T, Kamimura H: Identification of human UDP-glucuronosyltransferase responsible fbr the glucuronidation of niflumic acid in human liver. Pharm. Res. 23, 1502-1508 (2006).
189. Nishiyama T, Kobori T, Arai K et al.: Identification of human UDP-glucuronosyltransferase isoform(s) responsible for the C-glucuronidation of phenylbutazone. Arch. Biochem. Biophys. 454, 72-79 (2006).
190. Miners JO, Mackenzie PI: Drug glucuronidation in humans. Pharmacol. Ther. 51, 347-369 (1991).
191. Levesque E, Beaulieu M, Hum DW, Belanger A: Characterization and substrate specificity of UGT2B4 (E458): a UDP-glucuronosyltransferase encoded by a polymorphic gene. Pharmacogenetics 9, 207-216 (1999).
192. Nagar S, Zalatoris JJ, Blanchard RL: Human UGT1A6 pharmacogenetics: identificationof a novel SNP, characterization of allele frequencies and functional analysis of recombinant allozymes in human liver tissues and in cultured cells. Pharmacogenetics 14, 487-499 (2004).
193. Mano Y, Usui T, Kamimura H: In vitro inhibitory effects of nonsteroidal anti-inflammatory drugs on UDP-glucuronosyltransferase 1A1-catalysed estradiol 3β-glucuronidation in human liver microsomes. Biopharm. Drug Dispos. 26, 35-39 (2005).
194. Mano Y, Usui T, Kamimura H: In vitro inhibitory effects of nonsteroidal anti-inflammatory drugs on 4-methlumbelliferone glucumidation in recombinant human UDP-glucuronosyltransferase 1A9-potent inhibition by niflumic acid. Biopharm. Drug Dispos. 27, 1-6 (2006).
195. Mano Y, Usui T, Kamimura H: Inhibitory potential of nonsteroidal anti-inflammatory drugs on UDP-glucuronosyltransferase 2B7 in human liver microsomes. Eur. J. Clin. Pharmacol. 63, 211-216 (2007).
196. Kuehl GE, Bigler J, Potter JD, Lampe JW: Glucuronidation of the aspirin metabolite salicylic acid by expressed UDP-glucuronosyltransferases and human liver microsomes. Drug Metab. Dispos. 34, 199-202 (2006).
197. Chen Y, Kuehl GE, Bigler J et al.: UGT1A6 polymorphism and salicylic glucuronidation following aspirin. Pharmacogenet. Genomics 17, 571-579 (2007).
198. Daly AK, Aithal GP, Leathart JB, Swainsbury RA, Dang TS, Day CP: Genetic susceptibility to diclofenac-induced hepatotoxicity: contribution of UGT2B7, CYP2C8, and ABCC2 genotypes. Gastroenterology 132, 272-281 (2007).
199. Court MH, Duan SX, von Moltke LL et al.: Interindividual variability in acetaminophen glucuronidation by human liver microsomes: identification of relevant acetaminophen UDP glucuronyltransferase isoforms. J. Pharmacol. Exp. Ther. 299, 98-106 (2001).
200. Kostrubsky SE, Sinclair JF, Strom SC et al.: Phenobarbital and phenytoin increased acetaminophen hepatotoxicity due to inhibition of UDP-glucuronosyltransferases in cultured human hepatocytes. Toxicol. Sci. 87, 146-155 (2005).
201. de Morais SM, Uetrecht JP, Wells PG: Decreased glucuronidation and increased bioactivation of acetaminophen in Gilbert's syndrome. Gastroenterology 102, 577-586 (1992).
202. Esteban A, Perez-Mateo M: Heterogeneity of paracetamol metabolism in Gilbert's syndrome. Eur. J. Drug. Metab. Pharmacokinet. 24, 9-13 (1999).
203. Ullrich D, Sieg A, Blume R, Bock KW, Schroter W, Bircher J: Normal pathways for glucuronidation, sulphation and oxidation of paracetamol in Gilbert's syndrome. Eur. J. Clin. Invest. 17, 237-240 (1987).
204. Rauchschwalbe SK, Zuhlsdorf MT, Wensing G, Kuhlmann J: Glucuronidation of acetaminophen is independent of UGT1A1 promotor genotype. Int. J. Clin. Pharmacol. Ther. 42, 73-77 (2004).
205. Tankanitlert J, Morales NP, Howard TA et al.: Effects of combined UDP-glucuronosyltransferase (UGT) 1A1*28 and 1A6*2 on paracetamol pharmacokinetics in β-thalassemia/ HbE. Pharmacology 79, 97-103 (2007).
206. Coffman BL, Rios GD, King CD, Tephly TR: Human UGT2B7 catalyzes morphine glucuronidation. Drug. Metab. Dispos. 25, 1-4 (1997).
207. Stone AN, Mackenzie PI, Galetin A, Houston JB, Miners JO: Isoform selectivity and kinetics of morphine 3- and 6-glucuronidation by human UDP-glucuronosyltransferases: evidence for atypical glucuronidation kinetics by UGT2B7. Drug. Metab. Dispos. 31, 1086-1089 (2003).
208. Paul D, Standifer KM, Inturrisi CE, Pasternak GW: Pharmacological characterization of morphine 6b glucuronide very potent morphine metabolite. J. Pharm. Exp. Ther. 251, 477-483 (1989).
209. Coffman BL, King CD, Rios GR, Tephly TR: The glucuronidation of opioids, other xenobiotics, and androgens by human UGT2B7Y(268) and UGT2B7H(268). Drug. Metab. Dispos. 26, 73-77 (1998).
210. Holthe M, Klepstad P, Zahlsen K et al.: Morphine glucuronide to morphine plasma ratios are unaffected by the UGT2B7 H268Y and UGT1A1*28 polymorphisms in cancer patients on chronic morphine therapy. Eur. J. Clin. Pharmacol. 58, 353-356 (2002).
211. Duguay Y, Baar C, Skorpen F, Guillemette C: A novel functional polymorphism in the uridine diphosphateglucuronosyltransferase 2B7 promoter with significant impact on promoter activity. Clin. Pharmacol. Ther. 75, 223-233 (2004).
212. Sawyer MB, Innocenti F, Das S et al.: A pharmacogenetic study of uridine diphosphate-glucuronyltransferase 2B7 in patients receiving morphine. Clin. Pharmacol. Ther. 73, 566-574 (2003).
213. Darbari DS, van Schaik RH, Capparelli EV, Rana S, McCarter R, van den Anker J: UGT2B7 promoter variant -840G>A contributes to the variability in hepatic clearance of morphine in patients with sickle cell disease. Am. J. Hematol. 83(3), 200-202 (2008).
214. Holthe M, Rakvag TN, Klepstad P et al.: Sequence variations in the UDP-glucuronyltransferase 2B7 gene: identification of 10 novel SNPs and analysis of their relevance to morphine glucuronidation in cancer patients. Pharmacogenomics J. 3, 17-26 (2003).
215. Court MH, Krishnaswamy S, Hao Q et al.: Evaluation of 3′-azido-3′-deoxythymidine, morphine, and codeine as probe substrates for UDP-glucuronosyltransferase 2B7 (UGT2B7) in human liver microsomes: specificity and influence of the UGT2B732 polymorphism. Drug Metab. Dispos. 31, 1125-1133 (2003).
216. Green MD, King CD, Mojarrabi B, Mackenzie PI, Tephly TR: Glucuronidation of amines and other xenobiotics catalyzed by expressed human UDP glucuronosyltransferase 1A3. Drug Metab. Dispos. 26, 507-512 (1999).
217. King CD, Green MD, Rios GR et al.: The glucuronidation of exogenous and endogenous compounds by stably expressed rat and human UDP-glucuronosyltransferase 1.1. Arch. Biochem. Biophys. 332, 92-100 (1996).
218. Trapnell CB, Klecker RW, Jamis-Dow C, Collins JM: Glucuronidation of 3′-azido-3′-deoxythymidine (zidovudine) by human liver microsomes: relevance to clinical pharmacokinetic interactions with atovaquone, fluconazole, methadone, and valproic acid. Antimicrob. Agents Chemother. 42, 1592-1596 (1998).
219. McCance-Katz EF, Rainey PM, Jatlow P, Friedland G: Methadone effects on zidovudine disposition (AIDS Clinical Trials Group 262). J. Acquir. Immune. Defic. Syndr. Hum. Retrovirol. 18, 435-443 (1998).
220. Zubieta JK, Heitzeg MM, Smith YR et al.: COMTVall58Met genotype affects μ-opioid neurotransmitter responses to a pain stressor. Science 299, 1240-1243 (2003).
221. Rakvag TT, Klepstad P, Baar C et al.: The Vall58Met polymorphism of the human catechol-O-Lmethyltransferase (COMT) gene may influence morphine requirements in cancer pain patients. Pain 116, 73-78 (2005).
222. Berthele A, Platzer S, Jochim B et al.: COMTVall08/158Met genotype affects the μ-opioid receptor system in the human brain: evidence from ligand-binding, G-protein activation and preproenkephalin mRNA expression. Neuroimage 28, 185-193 (2005).
223. Reyes-Gibby CC, Shete S, Rakvag T et al.: Exploring joint effects of genes and the clinical efficacy of morphine-for cancer pain: OPRM1 and COMT gene. Pain 130, 25-30 (2007).
224. Hoehe MR, Kopke K, Wendel B et al.: Sequence variability and candidate gene analysis in complex disease: association of μ-opioid receptor gene variation with substance dependence. Hum. Mol. Genet. 22, 2895-2908 (2000).
225. Crowly JJ, Oslin DW, Patkar AA et al.: A genetic association study of the μ opioid receptor and severe opioid dependence. Psychiatr. Genet. 13, 169-173 (2003).
226. Landau L, Cahana A, Smiley RM, Antonarakis SE, Blouin JL: Genetic variability of μ-opioid receptor an in obstetric population. Anesthesiology 100, 1030-1033 (2004).
227. Lötsch J. Skarke C, Grosch S, Darimont J, Schmidt H, Geisslinger G: The polymorphism A118G of the human μ-opioid receptor gene decreases the pupil constrictory effect of morphine-6-glucuronide but not that of morphine. Pharmacogenetics 12, 3-9 (2002).
228. Skarke C, Darimont J, Schmidt H, Geisslinger G, Lötsch J: Analgesic effects of morphine and morphine-6-glucuronide in a transcutaneous electrical pain model in healthy volunteers. Clin. Pharmacol. Ther. 73, 107-121 (2003).
229. Romberg R, Olofsen E, Sarton E, den Hartigh J, Taschner PE, Dahan A: Pharmacokinetic-pharmacodynamic modeling of morphine-6-glucuronide induced analgesia in healthy volunteers: absence of sex differences. Anesthesiology 100, 120-133 (2004).
230. Klepstadt P, Rakvag TT, Kaasa S et at.: The 118 A>G polymorphism in the human μ-opioid receptor gene may increase morphine requirements in patients with pain caused by malignant disease. Acta Anaesthesiol. Scand. 48, 1232-1239 (2004).
231. Chou WY, Wang CH, Liu PH, Liu CC, Tseng CC, Jawan B: Human opioid receptor A118G polymorphism affects intravenous patient-controlled analgesia morphine consumption after total abdominal hysterectomy. Anesthesiology 105, 334-337 (2006).
232. Chou WY, Yang LC, Lu HF et al.: Association of μ-opioid receptor gene polymorphism (A118G) with variations in morphine consumption for analgesia after total knee arthroplasty. Acta Anaesthesiol. Scand. 50, 787-792 (2006).
233. Campa D, Gioia A, Tomei A, Poli P, Barale R: Association of ABCB1/ MDR1 and OPRM1 gene polymorphisms with morphine pain relief, Clin. Pharmacal. Ther. 83(4), 559-566 (2009).
234. Ide S, Minami M, Ishihara K, Uhl GR, Sora I, Ikeda K: μ-opioid receptor-dependent and independent components in effects of tramadol. Neuropharmacology 51, 651-658 (2006).
235. Caraco Y, Maroz Y, Davidson E: Variability in alfentanil analgesia may be attributed to polymorphism in the μ-opioid receptor. Can. Pharmacol. Ther. 69, P63 (2001).
236. Oertel BG, Schmidt R, Schneider A, Geisslinger G, Lötsch J: The μ-opioid receptor gene polymorphism 118A>G depletes alfentanil-induced analgesia and protects against respiratory depression in homozygous carriers. Pharmacogenet. Genomics 16, 625-636 (2006).
237. Rees JL, Birch-Machin M, Flanagan N, Healy E, Phillips S, Todd C: Genetic studies of the human melanocortin-1 receptor. Ann. NY Acad. Sci. 885, 134-142 (1999).
238. Schaffer JV, Bolognia JL: The melanocortin-1 receptor: red hair and beyond. Arch. Dermatol. 137, 1477-1485 (2001).
239. Liem. EB, Lin CM. Suleman MI et al.: Anesthetic requirement is increased in redheads. Anesthesiology 101, 279-283 (2004).
240. Liem EB, Joiner TV, Tsueda K, Sessier DI: Increased sensitivity to thermal pain and reduced subcutaneous lidocaine efficacy in redheads. Anesthesiology 102, 509-514 (2005).
241. Mogil JS, Wilson SG, Chesler EJ et al.: The melanocortin-1 receptor gene mediates female-specific mechanisms of analgesia in mice and humans. Proc Natl Acad. Sci. USA 100, 4867-4872 (2003).
242. Mogil JS, Ritchie J, Smith SB et al.: Melanocortin-1 receptor gene variants affect pain and μ-opioid analgesia in mice and humans. J. Med. Genet. 42, 583-587 (2005).
243. Lee W, Kim RB: Transporters and renal drug elimination. Annu. Rev. Pharmacol. Taxicol. 44,137-166 (2004).
244. Uwai Y, Saito H, Inui K: Interaction between methotrexate and nonsteroidal anti-inflammatory drugs in organic anion transporter. Eur. J. Pharmacol. 409, 31-36 (2000).
245. Marzolini C, Tirona RG, Kim RB: Pharmacogenomics of the OATP and OAT families. Pharmacogenomics 5, 273-292 (2004).
246. Uwai Y, Taniguchi R, Motohashi H, Saito H, Okuda M, Inui K: Methotrexateloxoprofen interaction: involvement of human organic anion transporters hOAT1 and hOAT3. Drug Metab. Pharmacokinet. 19, 369-374 (2004).
247. Mulato, AS, Ho ES, Cihlar T: Nonsteroidal anti-inflammatory drugs efficiently reduce the transport and cytotoxicity of adefovir mediated by the human renal organic anion transporter 1. J. Pharmacol. Exp. Ther. 295, 10-15 (2000).
248. El-Sheikh AA, van den Heuvel JJ, Koenderink JB, Russel FG: Interaction of nonsteroidal anti-inflammatory drugs with multidrug resistance protein (MRP) 2/ABCC2- and MRP4/ABCC4-mediated methotrexate transport. J. Pharmacol. Exp. Ther. 320, 229-235 (2007).
249. Xiong H, Turner KC, Ward ES, Jansen PL, Brouwer KL: Altered hepatobiliary disposition of acetaminophen glucuronide in isolated perfused livers from multidrug resistance-associated protein 2-deficient TR(-) rats. J. Pharmacol. Fxp. Ther. 295, 512-518 (2000).
250. Hirouchi M, Suzuki H, Itoda M et al.: Characterization of the cellular localization, expression level, and function of SNP variants of MRP2/ABCC2. Pharm. Res. 21, 742-748 (2004).
251. Nagar S, Walther S, Blanchard RL: Sulfotransferase (SULT) 1A1 polymorphic variants *1, *2, and *3 are associated with altered enzymatic activity, cellular phenotype, and protein degradation. Mol. Pharmacol. 69, 2084-2092 (2006).
252. King RS. Ghosh AA, Wu J: Inhibition of human phenol and estrogen sulfatransferase by certain non-steroidal anti-inflammatory agents. Curr. Drug. Metab. 7, 745-753 (2006).
253. Ulrich CM. Bigler J, Sibert J, Greene EA, Sparks R, Carlson CS, Potter JD: Cyclooxygenase 1 (COX1) polymorphisms in Aftican-American and Caucasian populations. Human Mut. 20, 409-410 (2002).
254. Halushka MK, Walker LP, Halushka PV: Genetic variation in cyclooxygenase 1: effects on response to aspirin. Clin. Pharmacol. Ther. 73, 122-130 (2003).
255. Lee CR, Bottone FG Jr, Krahn JM et al.: Identification and functional characterization of polymorphisms in human cyclooxygenase- 1 (PTGS1). Pharmacogenet. Genomics. 17, 145-160 (2007).
256. Lee YS, Kim H, Wu TX, Wang XM, Dionne RA: Genetically mediated interindividual variation in analgesic responses to cyclooxygenase inhibitory drugs. Clin. Pharmacol. Ther. 79, 407-418 (2006).
257. Skarke C, Reus M, Schmidt R et al.: The cyclooxygenase 2 genetic variant -765G>C does not modulate the effects of celecoxib on prostaglandin E2 production. Clin. Pharmacol. Ther. 80, 621-632 (2006).
258. Codd EE, Sjamk RP, Schupsky JJ et al.: Serotonin and norepinephrine uptake inhibiting activity of centrally acting analgesics: structural determinants and role in antinociception. J. Pharmacol. Exp. Ther. 274, 1263-1270 (1995).
259. Small KM, Liggett SB: Identification and functional characterization of α(2)-adrenoreceptor polymorphisms. Trends Pharmacol. Sci. 22, 471-477 (2001).
260. Arcioni R, Della Rocca M, Romano S, Romano R, Pietropaoli P, Gasparetto A: Ondansetron inhibits the analgesic effect of tramadol: a possible 5-HT3 spinal receptor involvement in acute pain in humans. Anesth. Analg. 94, 1553-1557 (2002).
261. De Witte JL, Schoenmaekers B, Sessler SI, Deloof T: The analgesic efficacy of tramadol is impaired by concurrent administration of ondansetron. Anesth. Analg. 92, 1319-1321 (2001).
262. Rojas-Corrales MO, Ortega-Alvaro A, Gibert-Rahola J et al.: Pindolol, a β-adrenoreceptor blocker/5-hydroxytryptamine (1A/1B) antagonist, enhances the analgesic effect of tramadol. Pain 88, 119-124 (2000).
263. Raffa RB, Friderichs E, Reimann W et al.: Opioid and non opioid components independently contribute to the mechanism of action of tramadol, an 'atypical' opioid analgesic. J. Pharmacol. Exp. Ther. 260, 275-285 (1992).
264. Oliva P, Aurilio C, Massimo F et al.: The antinociceptive effect of tramadol in the formalin test is mediated by the serotoninergic component. Eur. J. Pharmacol. 445, 179-185 (2002).
265. Ozdogan UK, Lahdesmaki J, Scheinin M: The analgesic efficacy of partial oploid agonists is increased in mice with targeted inactivation of α2A-adrenoreceptor gene. Eur. J. Pharmacol 529, 105-113 (2006).