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 following an oral dose of bupropion (150 mg) administered before and after rifampin treatment for 7 days in 35 healthy subjects. The AUC ratio of hydroxybupropion to bupropion in CYP2B6*6 carriers was significantly lower than that in CYP2B6*6 non-carriers 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 non-carriers, in the induced state (11.9 vs. 20.3, p= 0.045). The percentage difference in the AUC ratio between the basal and induced states was also significantly different (212% vs. 58.8%, p = 0.006). However, no significant difference was observed among the NR1I2 TGT genotypes for the CYP2B6*6 non-carriers (n = 22). In conclusion, it is suggested the NR1I2 TGT genotype decrease the bupropion hydroxylation induced by treatment with rifampin, particularly in CYP2B6*6 carriers.
- Received July 6, 2010.
- Accepted September 28, 2010.
- The American Society for Pharmacology and Experimental Therapeutics