S-Space College of Medicine/School of Medicine (의과대학/대학원) Dept. of Medicine (의학과) Journal Papers (저널논문_의학과)
Effects of Pregnane X Receptor (NR1I2) and CYP2B6 Genetic Polymorphisms on the Induction of Bupropion Hydroxylation by Rifampin
- Chung, Jae Yong; Cho, Joo-Youn; Lim, Hyeong-Seok; Kim, Jung-Ryul; Yu, Kung-Sang; Lim, Kyoung Soo; Shin, Sang-Goo; Jang, In-Jin
- Issue Date
- Drug Metabolism and Disposition Vol.39 No.1, pp. 92-97
- 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.
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