Evaluation of Compound Kushen Injection on the Five CYP Isozymes in Rats using a Cocktail Method

The aim of this study was to assess the influence of Compound Kushen Injection (CKI) on the activities of the drug-metabolizing enzymes CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 in rats. The activities of CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 were measured using specific probe drugs. After pretreatment for 1 week with CKI or physiological saline (control group), probe drugs phenacetin (5.0 mg/kg; CYP1A2 activity), tolbutamide (1.0 mg/kg; CYP2C9 activity), omeprazole (10 mg/kg; CYP2C19 activity), metoprolol (20 mg/kg; CYP2D6 activity) and midazolam (10 mg/kg; CYP3A4 activity) were given to rats by oral administration. The blood was then collected at different time points for ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis. The data showed that CKI exhibited an inhibitory effect on CYP2D6 and CYP3A4 by increasing t(1/2),C-max and AUC((0-infinity)), and decreasing CL/F compared with those of the control group. However, no significant changes in CYP1A2, CYP2C9 and CYP2C19 activities were observed. In conclusion, the results indicate that CKI could inhibit CYP2D6 and CYP3A4, which may affect the disposition of medicines primarily dependent on these pathways. Our work may be the basis of related drug interactions in the clinic.