Fig. 5.
Use of the RCN model to dissect the role of liver versus gut in drug metabolism. Adult male RCN or wild-type (WT) mice (n = 3) were treated with either 3-MC (40 mg/kg in corn-oil, intraperitoneally, single dose) or β-naphthoflavone (BNF, 80 mg/kg in corn-oil, intraperitoneally, daily for 4 days). After 10 days the mice were administered midazolam, orally at 2.5 mg/kg, and a pharmacokinetic study carried out. Serial blood samples were taken from the tail vein at the time points shown and analyzed by liquid chromatography–tandem mass spectrometry for levels of parent drug. Green symbols represent wild-type mice (Por lox/lox) treated with 3-MC (squares) or BNF (triangles), and red symbols represent RCN mice (Por lox/lox + Cre CYP1A1) treated with 3-MC (squares) or BNF (triangles). Data shown are mean ± SD. The table lists the pharmacokinetic parameters and associated statistical significance.