Evaluation of impact of Herba Erigerontis injection, a Chinese herbal prescription, on rat hepatic cytochrome P450 enzymes by cocktail probe drugs

摘要

Ethnopharmacological relevance: Herba Erigerontis injection (HEI), one of the most popular herbal prescription in China, is made from the aqueous extracts of Erigeron breviscapus whole plant. Now HEI is widely used for the treatment of cardiovascular diseases and cerebrovascular diseases such as coronary heart disease, anginapectoris and paralysis. Aim of the study: The purpose of this study was to investigate the in vivo effect of HEI on rat cytochrome P450 enzymes (CYP1A2, CYP2C11, CYP2D4, CYP2E1 and CYP3A2) to assess its safety through its potential to interact with co-administered drugs. Materials and methods: Rats were randomly divided into five groups. Rats were intravenous administrated with HEI via the caudal vein at the dosage of 1.8 ml/kg or 7.2 ml/kg once daily for consecutive 3 days or 14 days. On the fourth or the fifteenth day, a cocktail solution at a dose of 5 ml/kg, which contained caffeine (2.5 mg/kg), tolbutamide (2.5 mg/kg), chlorzoxazone (5 mg/kg), midazolam (5 mg/kg) and metoprolol (10 mg/kg), was injected via the lingual vein to all rats. Then 0.8 ml blood samples were collected at a set of time-points. The plasma concentrations of probe drugs were simultaneously determined by HPLC. Pharmacokinetic parameters simulated by DAS software were used for the evaluation of HEI on the activities of rat CYP1A2, CYP2C11, CYP2D4, CYP2E1 and CYP3A2 enzymes. ANOVA and Dunnett's test was used for data analysis. Results: There were no significant influence of pharmacokinetic parameters of caffeine, tolbutamide and chlorzoxazone in HEI pretreated rats. But many pharmacokinetic parameters of metoprolol and midazolam in HEI pretreated rats were affected significantly (P < 0.05), which indicated that metabolism of metoprolol and midazolam in these treatment groups was evidently slowed down. Conclusions: The results from the present in vivo study suggested that HEI showed no effects on rat CYP1A2, CYP2C11 and CYP2E1, however, it demonstrated potential inhibitory effects on rat CYP2D4 and CYP3A2. Therefore, caution is needed when HEI is co-administered with drugs metabolized by human CYP2D6 or CYP3A4 in clinic, which may result in increased concentrations of these drugs and relevant herb-drug interactions.