Effect of Darning Capsules on activity of cytochrome P450 in rats / 中国药学杂志

ABSTRACT

OBJECTIVE: To study the influence of Darning Capsules on cytochrome P450 activity in rats by using a "Cocktail" approach. METHODS: Rats were randomly divided into high-dose, low-dose and control groups. The rats in high-dose and low-dose groups were given 100 and 50 mg·kg-1 Darning Capsules, respectively, while the rats in the control group were given saline. The plasma concentrations of the probes were determined by HPLC methods. RESULTS: There were no significant differences in plasma concentrations and pharmacokinetic parameters of tolbutamide, metoprolol and chlorzoxazone between the control group and the test groups. Compared with the control group, high-dose Darning Capsules significantly increased the AUC, t1/2 and ρmax, and significantly decreased the VA/F and CL/F of caffeine and omeprazole. However, low-dose Darning Capsule did not induce significant changes in plasma concentrations and pharmacokinetic parameters of caffeine and omeprazole. The rats in high-dose and low-dose groups had higher AUC, t1/2 and ρmax, and lower Vd/F and CL/F for dapsone, compared with those in the control group. CONCLUSION: The results suggest that high-dose and low-dose Darning Capsules inhibit CYP3A4 activity, however, they have no effects on CYP2C9, CYP2D6 and CYP2E1. In addition, the activity of CYP1A2 and CYP2C19 can be inhibited by high-dose, but not low-dose Darning Capsules. Copyright 2012 by the Chinese Pharmaceutical Association.