In vitro inhibition of five traditional Chinese medicine injections on rat liver microsomal CYP3A

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 (TCMIs) in the present of testosterone, a specific substrate of CYP3A. 6beta-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 6beta-hydroxytestosterone by approximately 93.0%, which is more significant than other four TCMIs. The half maximal inhibitory concentration (IC50) and the enzyme-inhibitor constant K(i) 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.