RT Journal Article
SR Electronic
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
FD American Society for Pharmacology and Experimental Therapeutics
SP 92
OP 97
DO 10.1124/dmd.110.035246
VO 39
IS 1
A1 Jae Yong Chung
A1 Joo-Youn Cho
A1 Hyeong-Seok Lim
A1 Jung-Ryul Kim
A1 Kyung-Sang Yu
A1 Kyoung Soo Lim
A1 Sang-Goo Shin
A1 In-Jin Jang
YR 2011
UL http://dmd.aspetjournals.org/content/39/1/92.abstract
AB 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.