Characterization of cytochrome P450 (CYP3A12) induction by rifampicin in dog liver

1. Effects of rifampicin (Rif) on the contents of cytochrome P450 (P450) enzymes (CYP1A1/2, 2B11, 2C21 and 3A12) assessed by enzyme-linked immunosorbent assay and catalytic activities (ethoxyresorufin O-deethylase, and testosterone 6β-, 16α- and 16β-hydroxylase; 6β-, 16α- and 16β-OHT) in dog liver microsomes were compared between liver lobes of both the male and female dogs. 2. In the control dogs, the contents of individual P450 enzymes and their activities showed no significant differences between individual liver lobes and between the sexes. 3. Rif treatment (10 mg/kg/day, p.o. for 7 days) induced substantial increases in the content of CYP3A12 and 6β- and 16β-OHT activities, and slight increases in the content of CYP2B11 and 16α-OHT activity, and their elevated levels were virtually the same between liver lobes. The magnitudes of the elevation of the CYP3A12 level and 6β- and 16β-OHT activities compared with control levels appeared to be greater in the female dogs. However, the ratios of their magnitu...