Abstract
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. However, no statistically significant
difference among these pharmacokinetic parameters was detected for those
subjects carrying a CYP2B6 mutant with the exception of the tmax
of BUP, which showed a 1.61-fold increase among the feedingCYP2B6 mutant subjects relative to the fasting subjects.
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.
Keywords: high-fat diet, fasting and feeding, CYP2B6mutants, pharmacokinetics, bupropion, hydroxybupropion