Evaluation of effects of Chinese medicine Sailuotong on metabolic enzymes in rats by cocktail probe method

doi:10.12092/j.issn.1009-2501.2018.09.004

Abstract

Abstract:

AIM: To prevent drug interactions induced by the combination of drugs, the effects of Sailuotong, a traditional Chinese medicine compound used to treat vascular dementia, on main drug metabolic enzymes in rats were investigated. METHODS: After intragastric administration, the rats were given Sailuotong, and extract of ginseng, ginkgo leaf and crocus. They were then given cocktail of CYP1A2 (caffeine), CYP2C (omeprazole and losartan), CYP2D2 (dextromethorphan) and CYP1A1/2 (midazolam) probes. The blood drug concentration of each probe and specific metabolic substrate at different time points after administration was measured. The effects of single dose Sailuotong on the main CYP450 activity of rats were evaluated by analyzing the pharmacokinetic parameters and metabolic rate of the probe drug and its metabolite (the ratio of the metabolite to the probe AUC). RESULTS: Compared with the blank control, no statistically significant changes in the metabolic rate of each probe were found after single administration of Sailuotong (P>0.05). The peak time of caffeine probe drug was significantly delayed, while the peak concentration of metabolites was significantly increased, and the metabolic rate was increased by 31%, which was consistent with the trend after administrating ginseng extract. The AUC value of dextromethorphan metabolite was significantly decreased by single dose Sailuotong, while the metabolic rate was decreased by 37%, which was mainly induced by ginkgo leaf extract. CONCLUSION: Main metabolic activity of CYP450s in rats was not significantly affected by single dose of Sailuotong. The whole change trend was consistent with the combined effect of compound prescription.

Key words: Sailuotong, CYP450, cocktail probe, rat

CLC Number:

R965.2

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