摘要
目的:考察清开灵注射剂、金纳多注射剂、疏血通注射剂、参麦注射剂、康艾注射剂这5种临床常用的中药注射剂对大鼠肝微粒体CYP3A的体外抑制作用,预测发生药物相互作用的可能性,以确保这些中药注射剂临床应用的安全性与有效性。方法:采用SD大鼠肝微粒体体外孵育法,在孵育体系中加入底物睾酮和不同体积的清开灵注射剂等5种中药注射剂,用高效液相色谱法测定睾酮的羟化代谢产物6β-羟基睾酮的生成量反映CYP3A的活性,酮康唑用作阳性对照药。结果:在体外孵育体系中,10%的清开灵注射剂大约能抑制93.0%的6β-羟基睾酮生成,抑制效果明显高于其他4种相同浓度的中药注射剂。根据其抑制动力学曲线,计算出清开灵注射剂的IC50和Ki值分别为1.0%和0.7%。结论:在体外系统中,金纳多注射剂和疏血通注射剂对大鼠肝微粒体CYP3A无抑制作用,参麦注射剂和康艾注射剂对CYP3A显示出弱的抑制作用,清开灵注射剂对CYP3A有明显的抑制作用。提示当清开灵注射剂与经CYP3A代谢的药物联合用药时可能会发生药物相互作用,临床联合用药须谨慎。
Objective： Qingkailing injection （QKLI）, Jinnaduo injection （JNDI）, Shuxuetong injection （SXTI）, Shenmai injection （SMI） and Kangai injection （KAI） are widely used in China. To predict the herb-drug interactions in clinical application, they were evaluated for their in vitro inhibition effect on CYP3A in rat liver microsomes. Method： The rat liver microsomes were incubated with different doses of 5 kinds of traditional Chinese medicine injections （TCMls） in the present of testosterone, a specific snhstrate of CYP3A. 6β-hydroxytestosterone, the metabolite of testosterone, was monitored by HPLC to compare the inhibition effect of 5 TCMIs on CYP3A in rat liver microsomes. Ketoconazole was used as a positive control. Result： 10% QKLI reduced the formation of 6β-hydroxytestos- terone by approximately 93.0%, which is more significant than other four TCMIs. The half maximal inhibitory concentration （IC50） and the enzym-inhibotor constant Ki were 1.0% and 0.7% respectively. Conclusion： QKLI showed much stronger inhibition activity against CYP3A, comparing to other 4 TCMIs. The results revealed that QKLI may be involved in herb-drug interactions by inhibition of CYP3A.
出处
《中国中药杂志》
CAS
CSCD
北大核心
2011年第4期492-495,共4页
China Journal of Chinese Materia Medica
基金
国家"十一五"科技重大专项(2009ZX09502-021)
