BACKGROUND Genetic variability may influence methadone metabolism, dose requirements, and risk of relapse. OBJECTIVES To determine whether the CYP2B6*6 or ABCB1 (rs1045642) polymorphisms are associated with variation in methadone response (plasma concentration, dose, or response to treatment). METHODS Two independent reviewers searched Medline, EMBASE, CINAHL, PsycINFO, and Web of Science d...

BACKGROUND Metabolism and clearance of racemic methadone are stereoselective and highly variable, yet the mechanism remains largely unknown. Initial in vitro studies attributed methadone metabolism to cytochrome P4503A4 (CYP3A4). CYP3A4 was also assumed responsible for methadone clearance in vivo. Nevertheless, recent clinical data do not support a primary role for CYP3A4 and suggest that CYP2B...

This article has not been copyedited and formatted. The final version may differ from this version. #42176 3 ionization; LC-MS, liquid chromatography-mass spectrometry; LC-MS/MS, liquid chromatography-tandem mass spectrometry. This article has not been copyedited and formatted. The final version may differ from this version. Abstract The mechanism-based inactivation of human CYP2B6 by tert-buty...

OBJECTIVES To assess the effect of the major efavirenz metabolizing enzyme (CYP2B6) genotype and the effects of rifampicin co-treatment on induction of CYP3A by efavirenz. PATIENTS AND METHODS Two study arms (arm 1, n = 41 and arm 2, n = 21) were recruited into this study. In arm 1, cholesterol and 4β-hydroxycholesterol were measured in HIV treatment-naive patients at baseline and then at 4 a...

The mechanism-based inactivation of human CYP2B6 by tert-butylphenylacetylene (BPA) in the reconstituted system was investigated. The inactivation of CYP2B6 by BPA is time-, concentration-, and NADPH-dependent and exhibits a K(I) of 2.8 μM, a k(inact) of 0.7 min(-1), and a t(1/2) of 1 min. The partition ratio is ∼5. Unlike CYP2B1 and CYP2B4, in addition to the formation of an apoprotein adduct ...

Bupropion sustained release is used to promote smoking cessation in males and nonpregnant females. However, its efficacy as a smoking cessation aid during pregnancy is not reported. The pregnancy-associated changes in maternal physiology may alter the pharmacokinetics and pharmacodynamics of bupropion and consequently its efficacy in pregnant smokers. Therefore, the aims of this study were to d...

Due to the importance of in vitro cytochrome P450 (P450) induction assay to assess the possible drug-drug interaction events, the recent US Food and Drug Administration draft guidance and European Medicines Agency guideline recommend to assess P450 induction using fresh or cryopreserved hepatocytes at mRNA level and/or enzyme activity level. Although cryopreserved hepatocytes are commercially a...

Human upcyte® hepatocytes are proliferating hepatocytes that retain many characteristics of primary human hepatocytes. We conducted a comprehensive evaluation of the application of second-generation upcyte® hepatocytes from four donors for inhibition and induction assays using a selection of reference inhibitors and inducers. CYP1A2, CYP2B6, CYP2C9, and CYP3A4 were reproducibly inhibited in a c...

Abstract Background Human cytochrome P450 2B6 (CYP2B6) is fortified with the biotransformation of antimalarial, artemisinin combination therapy (ACT). Owing to emerging reports Plasmodium species resistance ACT in other climes, CYP2B6*6 genotype significantly alters metabolism. In North-Central Nigeria, distribution variant poorly documented. This study investigated CYP2B6 c.516G>T variants ...