Effects of high-fat diet and CYP2B6 mutants on the pharmacokinetics of bupropion and hydroxybupropion among healthy chinese subjects

Aims To provide evidence for the clinically rational administration of bupropion (BUP), the effects of high-fat diet and CYP2B6 mutants on BUP and hydroxybupropion (HBUP) among 44 healthy Chinese subjects. Methods The concentrations of BUP and HBUP in plasma were determined with a high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) analysis. Genotypes were ascertained after amplified by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Results The maximum plasma concentration (Cmax) and time to Cmax (tmax) of BUP as well as the concentration–time curve (AUC(0→96)) and Cmax of HBUP all increased by 1.18-, 1.41-, 1.38-, and 1.33-fold in the feeding group relative to the fasting group, respectively. Interestingly, the Cmax and terminal half-life (t1/2) of BUP increased by 1.33- and 1.39-fold among those subjects carrying the CYP2B6*1/*1 genotype in the feeding group relative to those in the fasting group. Similarly, the apparent volume of distribution (Vd) and clearance (CL) of HBUP increased by 1.38- and 1.59-fold, respectively, while the Cmax and AUC(0→96) of HBUP decreased by 1.44- and 1.49-fold among those subjects carrying the CYP2B6*1/*1 genotype in the feeding group relative to those in the fasting group. Concliusion These data suggest that high-fat diet and CYP2B6 mutants can influence the pharmacokinetic parameters of BUP and HBUP, thereby offering clear evidence for the rational administration of BUP among Chinese subjects in clinical settings.