CYP2B6, CYP3A4, and CYP2C19 are responsible for the in vitro N-demethylation of meperidine in human liver microsomes

Drug Metabolism and Disposition

Volumn 32, Issue 9, 2004, Pages 930-936

  Ramírez, Jacqueline ^a   Innocenti, Federico ^a   Schuetz, Erin G ^b   Flockhart, David A ^c   Relling, Mary V ^b   Santucci, Raymond ^a   Ratain, Mark J ^a  

^a UNIVERSITY OF CHICAGO   (United States)

^b ST JUDE CHILDREN S RESEARCH HOSPITAL   (United States)

^c INDIANA UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYTOCHROME P450 2B6; CYTOCHROME P450 2C19; CYTOCHROME P450 3A; DRUG METABOLITE; ENZYME ANTIBODY; FLUVOXAMINE; KETOCONAZOLE; MEPHENYTOIN; MIDAZOLAM; NORPETHIDINE; PETHIDINE; PHENYTOIN; THIOTEPA;

ARTICLE; CONTROLLED STUDY; CORRELATION ANALYSIS; DRUG CLEARANCE; DRUG HYDROXYLATION; DRUG METABOLISM; ENZYME ASSAY; ENZYME INHIBITION; ENZYME MECHANISM; ENZYME SUBSTRATE; HUMAN; HUMAN TISSUE; IN VITRO STUDY; LIVER METABOLISM; LIVER MICROSOME; METHYLATION; PRIORITY JOURNAL;

ARYL HYDROCARBON HYDROXYLASES; CYTOCHROME P-450 ENZYME SYSTEM; FLUVOXAMINE; HUMANS; HYDROXYLATION; ISOENZYMES; KETOCONAZOLE; MEPERIDINE; MEPHENYTOIN; MICROSOMES, LIVER; MIXED FUNCTION OXYGENASES; OXIDOREDUCTASES, N-DEMETHYLATING; RECOMBINANT PROTEINS; THIOTEPA;

STAPHYLOCOCCUS PHAGE 3A;

EID: 4143113867     PISSN: 00909556     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (41)

1. 6]ethanol: preliminary in vitro findings using a rat liver preparation. J Pharm Sci 86:1494-1496.
2. Chang TK, Bandiera SM, and Chen J (2003) Constitutive androstane receptor and pregnane X receptor gene expression in human liver: interindividual variability and correlation with CYP2B6 mRNA levels. Drug Metab Dispos 31:7-10.
3. Clark RF, Wei EM, and Anderson PO (1995) Meperidine: therapeutic use and toxicity. J Emerg Med 13:797-802.
4. De Rienzo F, Fanelli F, Menziani MC. and De Benedetti PG (2000) Theoretical investigation of substrate specificity for cytochromes P450 IA2, P450 IID6 and P450 IIIA4. J Comput-Aided Mol Des 14:93-116.
5. Ekins S, Vandenbranden M, Ring BJ, Gillespie JS, Yang TJ, Gelboin HV, and Wrighton SA (1998) Further characterization of the expression in liver and catalytic activity of CYP2B6. J Pharmacol Exp Ther 286:1253-1259.
6. 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.
7. Goldstein JA (2001) Clinical relevance of genetic polymorphisms in the human CYP2C family. Br J Clin Pharmacol 52:349-355.
8. Jinno H, Tanaka-Kagawa T, Ohno A, Makino Y, Matsushima E, Hanioka N, and Ando M (2003) Functional characterization of cytochrome P450 2B6 allelic variants. Drug Metab Dispos 31:398-403.
9. Kassahun K, Mcintosh IS, Shou M, Walsh DJ, Rodeheffer C, Slaughter DE, Geer LA, Halpin RA, Agrawal N, and Rodrigues AD (2001) Role of human liver cytochrome P4503A in the metabolism of etoricoxib, a novel cyclooxygenase-2 selective inhibitor. Drug Metab Dispos 29:813-820.
10. Ko J, Sukhova N, Thacker D, Chen P, and Flockhart DA (1997) Evaluation of omeprazole and lansoprazole as inhibitors of cytochrome P450 isoforms. Drug Metab Dispos 25:853-862.
11. Kuehl P, Zhang J, Lin Y, Lamba J, Assem M, Schuetz J, Watkins PB, Daly A, Wrighton SA, Hall SD, et al. (2001) Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression. Nat Genet 27:383-391.
12. Lamba V, Lamba J, Yasuda K, Strom S, Davila JC, Hancock M, Fackenthal JD, Rogan P, Ring BJ, Wrighton SA, and Schuetz EG (2003) Hepatic CYP2B6 expression: gender and ethnic differences and relationship to CYP2B6 genotype and CAR expression. J Pharmacol Exp Ther 307:906-922.
13. Lang T, Klein K, Fischer J, Nussler AK, Neuhaus P, Hofmann U, Eichelbaum M, Schwab M, and Zanger UM (2001) Extensive genetic polymorphism in the human CYP2B6 gene with impact on expression and function in human liver. Pharmacogenetics 11:399-415.
14. Lapple F, von Richter O, Fromm MF, Richter T, Thon KP, Wisser H, Griese EU, Eichelbaum M, and Kivisto KT (2003) Differential expression and function of CYP2C isoforms in human intestine and liver. Pharmacogenetics 13:565-575.
15. Lewis DF (2003) Essential requirements for substrate binding affinity and selectivity toward human CYP2 family enzymes. Arch Biochem Biophys 409:32-44.
16. Mankowski DC (1999) The role of CYP2C19 in the metabolism of (+/-) bufuralol, the prototypic substrate of CYP2D6. Drug Metab Dispos 27:1024-1028.
17. Martin H, Sarsat JP, de Waziers I, Housset C, Balladur P, Beaune P, Albaladejo V, and Lerche-Langrand C (2003) Induction of cytochrome P450 B6 and 3A4 expression by phenobarbital and cyclophosphamide in cultured human liver slices. Pharm Res (NY) 20:557-568.
18. Meatherall RC, Guay DR, and Chalmers JL (1985) Analysis of meperidine and normeperidine in serum and urine by high-performance liquid chromatography. J Chromatogr 338:141-149.
19. 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.
20. Pascussi JM, Gerbal-Chaloin S, Drocourt L, Maurel P, and Vilarem MJ (2003) The expression of CYP2B6, CYP2C9 and CYP3A4 genes: a tangle of networks of nuclear and steroid receptors. Biochim Biophys Acta 1619:243-253.
21. Payne VA, Chang YT, and Loew GH (1999) Homology modeling and substrate binding study of human CYP2C18 and CYP2C19 enzymes. Proteins 37:204-217.
22. Plotnikoff NP, Way EL, and Elliott HW (1956) Biotransformation products of meperidine excreted in the urine of man. J Pharmacol Exp Ther 117:414-419.
23. Pond SM and Kretschzmar KM (1981) Effect of phenytoin on meperidine clearance and normeperidine formation. Clin Pharmacol Ther 30:680-686.
24. Rae JM, Soukhova NV, Flockhart DA, and Zeruesenay D (2002) Triethylenethiophosphoramide is a specific inhibitor of cytochrome P450 2B6: implications for cyclophosphamide metabolism. Drug Metab Dispos 30:525-530.
25. Rasmussen BB, Nielsen TL, and Brosen K (1998) Fluvoxamine inhibits the CYP2C19-catalysed metabolism of proguanil in vitro. Eur J Clin Pharmacol 54:735-740.
26. Relling MV, Nemec J, Schuetz EG, Schuetz JD, Gonzalez FJ, and Korzekwa KR (1994) O-Demethylation of epipodophyllotoxins is catalyzed by human cytochrome P450 3A4. Mol Pharmacol 45:352-358.
27. Rodrigues AD (1999) Integrated cytochrome P450 reaction phenotyping: attempting to bridge the gap between cDNA-expressed cytochromes p450 and native human liver microsomes (Review). Biochem Pharmacol 57:465-480.
28. Roy JD, Girard M, and Drolet P (2004) Intrathecal meperidine decreases shivering during cesarean delivery under spinal anesthesia. Anesth Analg 98:230-234.
29. Roy P, Yu LJ, Crespi CL, and Wasman DJ (1999) Development of a substrate-activity based approach to identify the major human liver P-450 catalysts of cyclophosphamide and ifosfamide activation based on cDNA-expressed activities and liver microsomal P-450 profiles. Drug Metab Dispos 27:655-666.
30. Shiraga T, Kaneko H, Iwasaki K, Tozuka Z, Suzuki A, and Hata T (1999) Identification of cytochrome P450 enzymes involved in the metabolism of zotepine, an antipsychotic drug, in human liver microsomes. Xenobiotica 29:217-239.
31. Simopoulos TT, Smith HS, Peeters-Asdourian C, and Stevens DS (2002) Use of meperidine in patient-controlled analgesia and the development of a normeperidine toxic reaction. Arch Surg 137:84-88.
32. Stambaugh JE, Hemphill DM, Wainer IW, and Schwartz I (1977) A potentially toxic drug interaction between pethidine (meperidine) and phenobarbitone. Lancet 1:398-399.
33. Stambaugh JE, Wainer IW, and Schwartz I (1978) The effect of phenobarbital on the metabolism of meperidine in normal volunteers. J Clin Pharmacol 18:482-490.
34. Suzuki H, Kneller MB, Haining RL, Trager WF, and Rettie AE (2002) (+)-N-3-Benzyl-nirvanol and (-)-N-3-benzyl-phenobarbital: new potent and selective in vitro inhibitors of CYP2C 19. Drug Metab Dispos 30:235-239.
35. Thummel KE and Wilkinson GR (1998) In vitro and in vivo drug interactions involving human CYP3A. Annu Rev Pharmacol Toxicol 38:389-430.
36. Venkatakrishnan K, Von Moltke LL, Court MH, Harmatz JS, Crespi CL, and Greenblatt DJ (2000) Comparison between cytochrome P450 (CYP) content and relative activity approaches to scaling from cDNA-expressed CYPs to human liver microsomes: ratios of accessory proteins as sources of discrepancies between the approaches. Drug Metab Dispos 28:1493-1504.
37. Venkatakrishnan K, Von Moltke LL, and Greenblatt DJ (2001) Human drug metabolism and the cytochromes P450: application and relevance of in vitro models (Review). J Clin Pharmacol 41:1149-1179.
38. Wang Q and Halpert JR (2002) Combined three-dimensional quantitative structure-activity relationship analysis of cytochrome P450 2B6 substrates and protein homology modeling. Drug Metab Dispos 30:86-95.
39. Xie HJ, Yasar U, Lundgren S, Griskevicius L, Terelius Y, Hassan M, and Rane A (2003) Role of polymorphic human CYP2B6 in cyclophosphamide bioactivation. Pharmacogenomics J 3:53-61.
40. Yang TJ, Krausz KW, Sai Y, Gonzalez FJ, and Gelboin HV (1999) Eight inhibitory monoclonal antibodies define the role of individual P450s in human liver microsomal diazepam, 7-ethoxy-coumarin and imipramine metabolism. Drug Metab Dispos 27:102-109.
41. Zhang J, Bumell JC, Dumaual N, and Bosron WF (1999) Binding and hydrolysis of meperidine by human liver carboxylesterase hCE-1. J Pharmacol Exp Ther 290:314-318.