Losartan (LST) is a common chemical drug that is used to treat high blood pressure and reduce the risk of stroke in some people suffering from heart disease. Danshen, prepared from the dried root and rhizome of Salvia miltiorrhiza Bunge, has been widely used for the prevention and treatment of various cardiovascular and cerebrovascular diseases. There are more than 35 formulations with Danshen indicated in the Chinese Pharmacopoeia 2010, which are often combined with LST to treat cardiovascular and cerebrovascular diseases in the clinic. The effects of the two main components of Dansen,
salvianolic acid B (SA-B) and Tanshinon IIA (Tan IIA) on the pharmacokinetics of losartan and its metabolites in rats were EXP3174 by liquid chromatography with mass spectrometry (LC clerk). Sprague-Dawley rats were randomly assigned to 3 groups: LST, LST + the main pharmacokinetic parameters SA-B and LST + Tan IIA, and were estimated by oral administration of LST, LST + SA-B and LST + Tan IIA. It was found that there were significant differences in the pharmacokinetic parameters between the three groups: the LST + SA-B group was Cmax, t1 / 2, AUC, AUMC lower than that in the LST group then more in the LST group + Tan IIA. In addition, the effects of SA-B and II Tan on losartan metabolism were also examined using rat liver microsomes in vitro. The results showed that SA-B can induce LST Tan metabolism while IIA can inhibit LST metabolism in rat liver microsomes in vitro by regulating the activities of CYP450 enzymes. In addition, the effect of SA-B and Tan AII on CYP3A4 and CYP2C9 expression in Chang hepatic cells was examined by Western blotting and real-time PCR. It has been noted that the two components of Danshen, SA-B and Tan IIA different influences have on LST metabolism: SA-B can obviously speed up LST metabolism by inducing CYP3A4 / 2C9 activities and production, however, Tan IIA slow down the metabolism of LST by inhibiting CYP3A4 / 2C9 activities.
