Influence of CYP2B6 genetic variants on plasma and urine concentrations of bupropion and metabolites at steady state

Pharmacogenetics and Genomics

Volumn 23, Issue 3, 2013, Pages 135-141

  Benowitz, Neal L ^a   Zhu, Andy Z X ^b   Tyndale, Rachel F ^b   Dempsey, Delia ^a   Jacob III, Peyton ^a  

^a San Francisco   (United States)

^b UNIVERSITY OF TORONTO   (Canada)

Author keywords

bupropion; depression; genetic variants; metabolism; smoking cessation

Indexed keywords

AMFEBUTAMONE; CYTOCHROME P450 2B6; ERYTHROHYDROBUPROPION; NORADRENALIN UPTAKE INHIBITOR; RADAFAXINE; THREOHYDROBUPROPION; UNCLASSIFIED DRUG;

ADULT; AREA UNDER THE CURVE; ARTICLE; BLOOD SAMPLING; CONTROLLED STUDY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG METABOLISM; DRUG URINE LEVEL; FEMALE; GENE EXPRESSION; GENETIC ANALYSIS; GENETIC VARIABILITY; GENOTYPE; HUMAN; HUMAN EXPERIMENT; MALE; MAXIMUM PLASMA CONCENTRATION; METABOLITE; NORMAL HUMAN; PHARMACOGENETICS; PRIORITY JOURNAL; STEADY STATE; SUSTAINED DRUG RELEASE; URINALYSIS;

EID: 84873405931     PISSN: 17446872     EISSN: 17446880     Source Type: Journal    
DOI: 10.1097/FPC.0b013e32835d9ab0     Document Type: Article

References (31)

1. Johnston AJ, Ascher J, Leadbetter R, Schmith VD, Patel DK, Durcan M, et al. Pharmacokinetic optimisation of sustained-release bupropion for smoking cessation. Drugs 2002; 62 (Suppl 2):11-24.
2. Jefferson JW, Pradko JF, Muir KT. Bupropion for major depressive disorder: pharmacokinetic and formulation considerations. Clin Ther 2005; 27:1685-1695.
3. Damaj MI, Carroll FI, Eaton JB, Navarro HA, Blough BE, Mirza S, et al. Enantioselective effects of hydroxy metabolites of bupropion on behavior and on function of monoamine transporters and nicotinic receptors. Mol Pharmacol 2004; 66:675-682.
4. Damaj MI, Grabus SD, Navarro HA, Vann RE, Warner JA, King LS, et al. Effects of hydroxymetabolites of bupropion on nicotine dependence behavior in mice. J Pharmacol Exp Ther 2010; 334:1087-1095.
5. Bondarev ML, Bondareva TS, Young R, Glennon RA. Behavioral and biochemical investigations of bupropion metabolites. Eur J Pharmacol 2003; 474:85-93.
6. Grabus SD, Carroll FI, Damaj MI. Bupropion and its main metabolite reverse nicotine chronic tolerance in the mouse. Nicotine Tob Res 2012; 14:1356-1361.
7. Findlay JW, Van Wyck Fleet J, Smith PG, Butz RF, Hinton ML, Blum MR, et al. Pharmacokinetics of bupropion, a novel antidepressant agent, following oral administration to healthy subjects. Eur J Clin Pharmacol 1981; 21:127-135.
8. Hesse LM, Venkatakrishnan K, Court MH, von Moltke LL, Duan SX, Shader RI, et al. CYP2B6 mediates the in vitro hydroxylation of bupropion: potential drug interactions with other antidepressants. Drug Metab Dispos 2000; 28:1176-1183.
9. Faucette SR, Hawke RL, Lecluyse EL, Shord SS, Yan B, Laethem RM, et al. Validation of bupropion hydroxylation as a selective marker of human cytochrome P450 2B6 catalytic activity. Drug Metab Dispos 2000; 28:1222-1230.
10. Faucette SR, Hawke RL, Shord SS, Lecluyse EL, Lindley CM. Evaluation of the contribution of cytochrome P450 3A4 to human liver microsomal bupropion hydroxylation. Drug Metab Dispos 2001; 29:1123-1129.
11. Chen Y, Liu HF, Liu L, Nguyen K, Jones EB, Fretland AJ. The in vitro metabolism of bupropion revisited: concentration dependent involvement of cytochrome P450 2C19. Xenobiotica 2010; 40:536-546.
12. Zanger UM, Klein K, Saussele T, Blievernicht J, Hofmann MH, Schwab M. Polymorphic CYP2B6: molecular mechanisms and emerging clinical significance. Pharmacogenomics 2007; 8:743-759.
13. Lee AM, Jepson C, Hoffmann E, Epstein L, Hawk LW, Lerman C, et al. CYP2B6 genotype alters abstinence rates in a bupropion smoking cessation trial. Biol Psychiatry 2007; 62:635-641.
14. Binnington MJ, Zhu AZ, Renner CC, Lanier AP, Hatsukami DK, Benowitz NL, et al. CYP2A6 and CYP2B6 genetic variation and its association with nicotine metabolism in South Western Alaska Native people. Pharmacogenet Genomics 2012; 22:429-440.
15. Kirchheiner J, Klein C, Meineke I, Sasse J, Zanger UM, Murdter TE, et al. Bupropion and 4-OH-bupropion pharmacokinetics in relation to genetic polymorphisms in CYP2B6. Pharmacogenetics 2003; 13:619-626.
16. Loboz KK, Gross AS, Williams KM, Liauw WS, Day RO, Blievernicht JK, et al. Cytochrome P450 2B6 activity as measured by bupropion hydroxylation: effect of induction by rifampin and ethnicity. Clin Pharmacol Ther 2006; 80:75-84.
17. Lamba V, Lamba J, Yasuda K, Strom S, Davila J, Hancock ML, et al. Hepatic CYP2B6 expression: gender and ethnic differences and relationship to CYP2B6 genotype and CAR (constitutive androstane receptor) expression. J Pharmacol Exp Ther 2003; 307:906-922.
18. Hofmann MH, Blievernicht JK, Klein K, Saussele T, Schaeffeler E, Schwab M, et al. Aberrant splicing caused by single nucleotide polymorphism c.516G > T [Q172H], a marker of CYP2B6&z.ast;6, is responsible for decreased expression and activity of CYP2B6 in liver. J Pharmacol Exp Ther 2008; 325:284-292.
19. Hesse LM, He P, Krishnaswamy S, Hao Q, Hogan K, von Moltke LL, et al. Pharmacogenetic determinants of interindividual variability in bupropion hydroxylation by cytochrome P450 2B6 in human liver microsomes. Pharmacogenetics 2004; 14:225-238.
20. Desta Z, Saussele T, Ward B, Blievernicht J, Li L, Klein K, et al. Impact of CYP2B6 polymorphism on hepatic efavirenz metabolism in vitro. Pharmacogenomics 2007; 8:547-558.
21. Klein K, Lang T, Saussele T, Barbosa-Sicard E, Schunck WH, Eichelbaum M, et al. Genetic variability of CYP2B6 in populations of African and Asian origin: allele frequencies, novel functional variants, and possible implications for anti-HIV therapy with efavirenz. Pharmacogenet Genomics 2005; 15:861-873.
22. Laizure SC, DeVane CL. Stability of bupropion and its major metabolites in human plasma. Ther Drug Monit 1985; 7:447-450.
23. Al Koudsi N, Tyndale RF. Hepatic CYP2B6 is altered by genetic, physiologic, and environmental factors but plays little role in nicotine metabolism. Xenobiotica 2010; 40:381-392.
24. Haas JS, Kaplan CP, Barenboim D, Jacob P 3rd, Benowitz NL. Bupropion in breast milk: an exposure assessment for potential treatment to prevent post-partum tobacco use. Tob Control 2004; 13:52-56.
25. Zhu AZ, Cox LS, Nollen N, Mayo M, Faseru B, Okuyemi KS, et al. CYP2B6 and bupropion's smoking cessation pharmacology: the role of hydroxybupropion. Clin Pharmacol Ther 2012; 96:771-777.
26. Petsalo A, Turpeinen M, Tolonen A. Identification of bupropion urinary metabolites by liquid chromatography/mass spectrometry. Rapid Commun Mass Spectrom 2007; 21:2547-2554.
27. Zhang H, Sridar C, Kenaan C, Amunugama H, Ballou DP, Hollenberg PF. 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 2011; 338:803-809.
28. Xu H, Loboz KK, Gross AS, McLachlan AJ. Stereoselective analysis of hydroxybupropion and application to drug interaction studies. Chirality 2007; 19:163-170.
29. Kharasch ED, Mitchell D, Coles R. Stereoselective bupropion hydroxylation as an in vivo phenotypic probe for cytochrome P4502B6 (CYP2B6) activity. J Clin Pharmacol 2008; 48:464-474.
30. Wang J, Sonnerborg A, Rane A, Josephson F, Lundgren S, Stahle L, et al. Identification of a novel specific CYP2B6 allele in Africans causing impaired metabolism of the HIV drug efavirenz. Pharmacogenet Genomics 2006; 16:191-198.
31. Ngaimisi E, Mugusi S, Minzi O, Sasi P, Riedel KD, Suda A, et al. Effect of rifampicin and CYP2B6 genotype on long-term efavirenz autoinduction and plasma exposure in HIV patients with or without tuberculosis. Clin Pharmacol Ther 2011; 90:406-413.