基于药代作用机制的参麦注射液用药配伍禁忌研究

The use of herbal injection in China is wide and escalating year by year, especially in the field of cardiovascular medicine. “Guidance of clinical investigation for safety re-evaluation of Traditional Chinese Medicine Injection” was recently published by China Food and Drug Administration. It is pointed out that the contraindication of herbal injection with drugs in common use clinically should be illustrated and the relevant information should be included in DRUG INTERACTIONS, WARININGS AND PRECAUTIONS, or CONTRAINDICATION sections of the labeling. Shenmai injection is made fromRadix Ginseng Rubra and Radix Ophiopogonis and used for the treatment of coronary heart diseases and viral myocarditis. Based on known rat pharmacokinetic information, Shenmai saponins were eliminated mainly by biliary excretion via liver and urinary excretion via kidney. The current study intended to characterize the molecular mechanism involved in the major elimination pathways of the saponins and to evaluate the inhibitory effects of saponins, that are highly exposed in liver or kidney, on the hepatic and kidney uptake and efflux transporters. In vivo pharmacokinetic interaction studies of Shenmai injection and commonly used drugs would be carried out based on in vitro findings. This study will contribute to fully characterize the contraindications of Shenmai injection.

中药注射剂在中国药品市场尤其是心血管药物中占有很大的比重，国家食品药品监督管理局发布的《中药注射剂安全性再评价临床研究评价技术原则（试行）》指出应“提供中药注射剂与临床常用药品的配伍禁忌，纳入说明书注意事项或相互作用项中”。参麦注射液由红参和麦冬组成,前期大鼠药代动力学研究提示,皂苷成分主要由经肝脏的胆汁排泄和经肾脏的尿排泄消除,并且在肝脏和肾脏中都观察到了一些暴露较高的成分。本项研究结合皂苷胆汁排泄中存在的主动分泌过程的分子作用机制，开展合用药物对参麦注射液的血浆、肝、肾暴露的影响研究。同时对那些具有较高肝肾暴露的成分进行对主要肝肾转运体的抑制活性筛查，对于围绕能被皂苷成分明确抑制的转运体，开展参麦注射液对这些转运体底物药物合用的影响研究。通过本项研究明确肝肾消除过程中相关转运体层面的参麦注射液与合用药物的相互作用可能性及程度，为参麦注射液的用药配伍禁忌提供数据。