TY - JOUR T1 - Effects of Pregnane X Receptor (<em>NR1I2</em>) and CYP2B6 Genetic Polymorphisms on the Induction of Bupropion Hydroxylation by Rifampin JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 92 LP - 97 DO - 10.1124/dmd.110.035246 VL - 39 IS - 1 AU - Jae Yong Chung AU - Joo-Youn Cho AU - Hyeong-Seok Lim AU - Jung-Ryul Kim AU - Kyung-Sang Yu AU - Kyoung Soo Lim AU - Sang-Goo Shin AU - In-Jin Jang Y1 - 2011/01/01 UR - http://dmd.aspetjournals.org/content/39/1/92.abstract N2 - 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. ER -