Differences in methadone metabolism by CYP2B6 variants

Drug Metabolism and Disposition

Volumn 43, Issue 7, 2015, Pages 994-1001

  Gadel, Sarah ^a   Friedel, Christina ^a   Kharasch, Evan D ^a,b  

^a Division of Clinical and Translational Research   (United States)

^b WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 ETHYLIDENE 1,5 DIMETHYL 3,3 DIPHENYLPYRROLIDINE; CYTOCHROME B5; CYTOCHROME P450 2B6; CYTOCHROME P450 REDUCTASE; GUANINE; METHADONE; THYMINE; ISOENZYME; NARCOTIC AGENT; RECOMBINANT PROTEIN;

ALLELE; ANIMAL CELL; ARTICLE; CATALYSIS; CONTROLLED STUDY; DEMETHYLATION; DRUG CLEARANCE; DRUG METABOLISM; GENETIC POLYMORPHISM; GENETIC VARIABILITY; IN VITRO STUDY; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; STEREOCHEMISTRY; ANIMAL; CELL CULTURE; GENETICS; HUMAN; INSECT; METABOLISM; METHYLATION; PLASMID; SPODOPTERA; STEREOISOMERISM;

HEXAPODA;

ALLELES; ANIMALS; CELLS, CULTURED; CYTOCHROME P-450 CYP2B6; CYTOCHROMES B5; HUMANS; INSECTS; ISOENZYMES; METHADONE; METHYLATION; NARCOTICS; PLASMIDS; RECOMBINANT PROTEINS; SPODOPTERA; STEREOISOMERISM;

EID: 84940426119     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.115.064352     Document Type: Article

References (52)

1. Ahuja S, Jahr N, Im S.C., Vivekanandan S., Popovych N, Le Clair SV, Huang R, Soong R, Xu J., and Yamamoto K, et al. (2013) A model of the membrane-bound cytochrome b5-cytochrome P450 complex from NMR and mutagenesis data. J Biol Chem 288:22080-22095.
2. Ariyoshi N, Ohara M, Kaneko M., Afuso S, Kumamoto T, Nakamura H., Ishii I, Ishikawa T, and Kitada M (2011) Q172H replacement overcomes effects on the metabolism of cyclo-phosphamide and efavirenz caused by CYP2B6 variant with Arg262. Drug Metab Dispos 39: 2045-2048.
3. Bruce RD, Moody DE, Altice F.L., Gourevitch MN, and Friedland GH (2013) A review of pharmacological interactions between HIV or hepatitis C virus medications and opioid agonist therapy: implications and management for clinical practice. Expert Rev Clin Pharmacol 6: 249-269.
4. Chang Y, Fang WB, Lin S.N., and Moody DE (2011) Stereo-selective metabolism of methadone by human liver microsomes and cDNA-expressed cytochrome P450s: a reconciliation. Basic Clin Pharmacol Toxicol 108:55-62.
5. Crettol S, Déglon JJ, Besson J., Croquette-Krokkar M, Gothuey I, Hämmig R, Monnat M., Hüttemann H, Baumann P., and Eap CB (2005) Methadone enantiomer plasma levels, CYP2B6, CYP2C19, and CYP2C9 genotypes, and response to treatment. Clin Pharmacol Ther 78:593-604.
6. Crettol S, Déglon JJ, Besson J., Croquette-Krokar M, Hämmig R, Gothuey I., Monnat M, and Eap CB (2006) ABCB1 and cytochrome P450 genotypes and phenotypes: influence on methadone plasma levels and response to treatment. Clin Pharmacol Ther 80:668-681.
7. Desta Z, Saussele T, Ward B., Blievernicht J, Li L, Klein K., Flockhart DA, and Zanger UM (2007) Impact of CYP2B6 polymorphism on hepatic efavirenz metabolism in vitro. Pharmacogenomics 8:547-558.
8. Dignam JD and Strobel HW (1977) NADPH-cytochrome P-450 reductase from rat liver: purification by affinity chromatography and characterization. Biochemistry 16:1116-1123.
9. Eap CB, Crettol S, Rougier J.S., Schläpfer J, Sintra Grilo L, Déglon JJ, Besson J., Croquette-Krokar M, Carrupt PA, and Abriel H (2007) Stereoselective block of hERG channel by (S)-methadone and QT interval prolongation in CYP2B6 slow metabolizers. Clin Pharmacol Ther 81: 719-728.
10. Ferrari A, Coccia CP, Bertolini A, and Sternieri E (2004) Methadone - metabolism, pharmaco-kinetics and interactions. Pharmacol Res 50:551-559.
11. 5. J Biol Chem 283:31385-31393.
12. Gadel S, Crafford A, Regina K., and Kharasch ED (2013) Methadone N-demethylation by the common CYP2B6 allelic variant CYP2B6.6. Drug Metab Dispos 41:709-713.
13. Gerber JG, Rhodes RJ, and Gal J (2004) Stereoselective metabolism of methadone N-demethylation by cytochrome P4502B6 and 2C19. Chirality 16:36-44.
14. Greenblatt DJ (2014) Drug interactions with methadone: Time to revise the product label. Clin Pharmacol Drug Dev 3:249-251.
15. Hildebrandt A and Estabrook RW (1971) Evidence for the participation of cytochrome b 5 in hepatic microsomal mixed-function oxidation reactions. Arch Biochem Biophys 143:66-79.
16. ∗6, is responsible for decreased expression and activity of CYP2B6 in liver. J Pharmacol Exp Ther 325:284-292.
17. Honda M, Muroi Y, Tamaki Y., Saigusa D, Suzuki N, Tomioka Y., Matsubara Y, Oda A, Hirasawa N., and Hiratsuka M (2011) Functional characterization of CYP2B6 allelic variants in demethylation of antimalarial artemether. Drug Metab Dispos 39:1860-1865.
18. Hung CC, Chiou MH, Huang B.H., Hsieh YW, Hsieh TJ, Huang CL, and Lane HY (2011) Impact of genetic polymorphisms in ABCB1, CYP2B6, OPRM1, ANKK1 and DRD2 genes on methadone therapy in Han Chinese patients. Pharmacogenomics 12:1525-1533.
19. Im SC and Waskell L (2011) The interaction of microsomal cytochrome P450 2B4 with its redox partners, cytochrome P450 reductase and cytochrome b(5). Arch Biochem Biophys 507: 144-153.
20. Kharasch ED and Stubbert K (2013a) Cytochrome P4503A does not mediate the interaction between methadone and ritonavir-lopinavir. Drug Metab Dispos 41:2166-2174.
21. Kharasch ED and Stubbert K (2013b) Role of cytochrome P4502B6 in methadone metabolism and clearance. J Clin Pharmacol 53:305-313.
22. Kharasch ED, Hoffer C, Whittington D., and Sheffels P (2004) Role of hepatic and intestinal cytochrome P450 3A and 2B6 in the metabolism, disposition, and miotic effects of methadone. Clin Pharmacol Ther 76:250-269.
23. Kharasch ED, Bedynek PS, Park S, Whittington D., Walker A, and Hoffer C (2008a) Mechanism of ritonavir changes in methadone pharmacokinetics and pharmacodynamics: I. Evidence against CYP3A mediation of methadone clearance. Clin Pharmacol Ther 84:497-505.
24. Kharasch ED, Mitchell D, Coles R., and Blanco R (2008b) Rapid clinical induction of hepatic cytochrome P4502B6 activity by ritonavir. Antimicrob Agents Chemother 52:1663-1669.
25. Kharasch ED, Bedynek PS, Hoffer C, Walker A., and Whittington D (2012) Lack of indinavir effects on methadone disposition despite inhibition of hepatic and intestinal cytochrome P4503A (CYP3A). Anesthesiology 116:432-447.
26. ∗6 genotype. Clin Pharmacol Ther 95:S53.
27. Lang T, Klein K, Fischer J., Nüssler 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.
28. Lee CA, Kadwell SH, Kost T.A., and Serabjit-Singh CJ (1995) CYP3A4 expressed by insect cells infected with a recombinant baculovirus containing both CYP3A4 and human NADPH-cytochrome P450 reductase is catalytically similar to human liver microsomal CYP3A4. Arch Biochem Biophys 319:157-167.
29. Levran O, Peles E, Hamon S., Randesi M, Adelson M, and Kreek MJ (2013) CYP2B6 SNPs are associated with methadone dose required for effective treatment of opioid addiction. Addict Biol 18:709-716.
30. ∗6 allele significantly alters the N-demethylation of ketamine enantiomers in vitro. Drug Metab Dispos 41:1264-1272.
31. Matsubara T, Koike M, Touchi A., Tochino Y, and Sugeno K (1976) Quantitative determination of cytochrome P-450 in rat liver homogenate. Anal Biochem 75:596-603.
32. McLaughlin LA, Ronseaux S, Finn R.D., Henderson CJ, and Roland Wolf C (2010) Deletion of microsomal cytochrome b5 profoundly affects hepatic and extrahepatic drug metabolism. Mol Pharmacol 78:269-278.
33. Mo SL, Liu YH, Duan W, Wei M.Q., Kanwar JR, and Zhou SF (2009) Substrate specificity, regulation, and polymorphism of human cytochrome P450 2B6. Curr Drug Metab 10: 730-753.
34. 5) in the expression system and the differences in the marker activities. J Pharm Sci 91:952-963.
35. 5. Pharmacogenet Genomics 23:41-52.
36. Parikh A, Gillam EM, and Guengerich FP (1997) Drug metabolism by Escherichia coli expressing human cytochromes P450. Nat Biotechnol 15:784-788.
37. Paulozzi LJ, Mack KA, and Jones CM; Centers for Disease Control and Prevention (CDC) (2012) Vital signs: risk for overdose from methadone used for pain relief - United States, 1999-2010. MMWR Morb Mortal Wkly Rep 61:493-497.
38. Raccor BS, Claessens AJ, Dinh J.C., Park JR, Hawkins DS, Thomas SS, Makar K.W., McCune JS, and Totah RA (2012) Potential contribution of cytochrome P450 2B6 to hepatic 4-hydroxy-cyclophosphamide formation in vitro and in vivo. Drug Metab Dispos 40:54-63.
39. Radloff R, Gras A, Zanger U.M., Masquelier C., Arumugam K, Karasi JC, Arendt V, Seguin-Devaux C, and Klein K (2013) Novel CYP2B6 enzyme variants in a Rwandese population: functional characterization and assessment of in silico prediction tools. Hum Mutat 34: 725-734.
40. Schenkman JB and Jansson I (2003) The many roles of cytochrome b5. Pharmacol Ther 97: 139-152.
41. Totah RA, Allen KE, Sheffels P, Whittington D., and Kharasch ED (2007) Enantiomeric metabolic interactions and stereoselective human methadone metabolism. J Pharmacol Exp Ther 321:389-399.
42. Totah RA, Sheffels P, Roberts T., Whittington D, Thummel K, and Kharasch ED (2008) Role of CYP2B6 in stereoselective human methadone metabolism. Anesthesiology 108:363-374.
43. Turpeinen M and Zanger UM (2012) Cytochrome P450 2B6: function, genetics, and clinical relevance. Drug Metabol Drug Interact 27:185-197.
44. van Heeswijk R., Verboven P, Vandevoorde A., Vinck P, Snoeys J, Boogaerts G., De Paepe E, Van Solingen-Ristea R, Witek J and Garg V (2013) Pharmacokinetic interaction between telaprevir and methadone. Antimicrob Agents Chemother 57:2304-2309.
45. Vourvahis M, Wang R, Gruener D.M., Bruce RD, Haider S, and Tawadrous M (2012) Effect of lersivirine co-administration on pharmacokinetics of methadone in healthy volunteers. Drug Alcohol Depend 126:183-188.
46. Wang H and Tompkins LM (2008) CYP2B6: new insights into a historically overlooked cyto-chrome P450 isozyme. Curr Drug Metab 9:598-610.
47. Wang SC, Ho IK, Tsou H.H., Tian JN, Hsiao CF, Chen CH, Tan H.K., Lin L., Wu CS, and Su LW, et al. (2011) CYP2B6 polymorphisms influence the plasma concentration and clearance of the methadone S-enantiomer. J Clin Psychopharmacol 31:463-469.
48. Watanabe T, Sakuyama K, Sasaki T., Ishii Y, Ishikawa M, Hirasawa N., and Hiratsuka M (2010) Functional characterization of 26 CYP2B6 allelic variants (CYP2B6.2-CYP2B6.28, except CYP2B6.22). Pharmacogenet Genomics 20:459-462.
49. 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.
50. ∗6 allele on catalytic properties and inhibition of CYP2B6 in vitro: implication for the mechanism of reduced efavirenz metabolism and other CYP2B6 substrates in vivo. Drug Metab Dispos 40:717-725.
51. Zanger UM and Klein K (2013) Pharmacogenetics of cytochrome P450 2B6 (CYP2B6): advances on polymorphisms, mechanisms, and clinical relevance. Front Genet 4:24.
52. Zhang H, Sridar C, Kenaan C., Amunugama H, Ballou DP, and Hollenberg PF (2011) Polymorphic variants of cytochrome P450 2B6 (CYP2B6.4-CYP2B6.9) exhibit altered rates of metabolism for bupropion and efavirenz: a charge-reversal mutation in the K139E variant (CYP2B6.8) impairs formation of a functional cytochrome p450-reductase complex. J Pharmacol Exp Ther 338:803-809.