Effects of Ougan juice on P450 activities using a cocktail method

Ougan (Citrus suavissima Hort. ex Tanaka) is an important domesticated fruit which is used medicinally in China. To date, a number of methods for its identification and chemical analysis have been studied. However, the effects of Ougan juice on CYP isozymes have not been reported. Therefore, the objective of our study was to evaluate the potential effects of Ougan juice on the CYP isozymes CYP1A2, CYP2C9, CYP2C19 and CYP2D6 in rats using a cocktail approach involving the probe drugs phenacetin, tolbutamide, omeprazole and dextromethorphan. These four probe drugs were simultaneously administered to rats after single and multiple dosing of Ougan juice by gastric irrigation. The pharmacokinetics of the probes in the plasma were simultaneously determined by HPLC-MS. The main pharmacokinetic parameters of the four probe drugs were not significantly different in rats after single dose of Ougan juice. The t1/2 and AUC(0-infinity) of phenacetin and omeprazole increased significantly and their CL(z) decreased markedly after multiple dosing of Ougan juice. However, the t1/2 of tolbutamide decreased notably, while the t1/2 of dextromethorphan was not changed. The findings of this study suggest that a single administration of Ougan juice had little effect on P450 activities while multiple administration of Ougan juice tended to inhibit CYP1A2 and CYP2C19 and induce CYP2C9, but did not influence CYP2D6.