Abstract
We investigated genetic polymorphisms in the pregnane X receptor (NR1I2) in Korean individuals (n = 83) and the effects of NR1I2 genotypes on rifampin-mediated induction of bupropion hydroxylation. The pharmacokinetics of bupropion and hydroxybupropion were evaluated after an oral dose of bupropion (150 mg) administered before and after rifampin treatment for 7 days in 35 healthy subjects. The area under the time-concentration curve (AUC) ratio of hydroxybupropion to bupropion in CYP2B6*6 carriers was significantly lower than that in CYP2B6*6 noncarriers in both the basal and rifampin-induced states (p = 0.012). Among the CYP2B6*6 carriers (n = 13), the NR1I2 TGT (−25385T + g.7635G + g.8055T) carriers exhibited a significantly lower AUC ratio, representing the CYP2B6 hydroxylation activity, compared with the TGT noncarriers, in the induced state (11.9 versus 20.3, p = 0.045). The percent difference in the AUC ratio between the basal and induced states was also significantly different (212% versus 58.8%, p = 0.006). However, no significant difference was observed among the NR1I2 TGT genotypes for the CYP2B6*6 noncarriers (n = 22). In conclusion, it is suggested the NR1I2 TGT genotype decreases the bupropion hydroxylation induced by treatment with rifampin, particularly in CYP2B6*6 carriers.
Footnotes
- Received July 2, 2010.
- Accepted September 28, 2010.
This study was supported by the Korea Healthcare Technology R&D Project, Ministry for Health and Welfare, Republic of Korea [Grant A030001].
Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.
doi:10.1124/dmd.110.035246.
ABBREVIATIONS:
- PXR
- pregnane X receptor
- SNP
- single-nucleotide polymorphism
- PK
- pharmacokinetics
- PCR
- polymerase chain reaction
- AUC_bup
- area under the time-concentration curve of bupropion
- AUC_hyd
- area under the time-concentration curve of hydroxybupropion
- CAR
- constitutive androstane receptor
- bp
- base pair.
- Copyright © 2011 by The American Society for Pharmacology and Experimental Therapeutics
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