Study On The Influence Of Ginsenoside Re On Cytochrome P450 Isoforms By Cocktail Approach Using Probe Drugs

Aim: To study the influence of Ginsenoside Re on cytochrome P450 isoforms CYP3A4, CYP1A2, CYP2E1, CYP2C19, thus provide a guide for clinical treatment.Methods: In the study, a "Cocktail" approach in rats by HPLC was established and validated to evaluate the inductive or inhibitory effects on CYP3A4, CYP1A2, CYP2E1. CYP2C19 by pharmacokinetic parameters of four probe drugs dapsone, caffeine, chlorzoxazone and omeprazole. The results of validation showed that the established methods were suitable for bioanalysis. Rats were randomly divided into control group and test group and two procedures were adopted. Ginsenoside Re were administered orally for five days at a dose of 2.5 mg kg-1 body weight for test group and water were administered in the same way for control group. On the sixth day, probe drugs dapsone and caffeine were administered by caudal vein iv. at a dose of 10 mg kg-1 body weight for both of groups. In another procedure, chlorzoxazone and omeprazole were administered in the same way. the blood sample were taken from eyeball at 0.183, 0.25, 0.5, 0.75, 1, 2, 5, 8 and 12h After administration of dapsone and caffeine, and at 2, 5, 10, 15, 30, 45, 60, 120, 180 and 300 min after administration of chlorzoxazone and omeprazole. The concetration-time data were fitted by 3P97 Pharmacokinetic Programe and the mainpharmacokinetic parameters were calculated by this program. The effects of Ginsenoside Re on cytochrome P450 isoforms CYP3A4, CYP1A2^ CYP2EK CYP2C19 were observed indirectly by Comparing the pharmacokinetic parametert1/2BResults: The T1/2B of four probe drugs were : dapsone: 5.75, 7.41h; caffeine: 2.88, 3.45h; chlorzoxazone: 55.68, 53.22min; omeprazole: 14.64, 16.11min between test group and control group respectively. The t1/2B of caffeine and dapsone between test group and control group had significance difference by Student1 s /test, and that of chlorzoxazone and omeprazole did not have significance difference.Conclusion: The results suggested that Ginsenoside Re could induce CYP1A2 and CYP3A4, and had no influence on CYP2E1 and CYP2C19.