Effects of Xuesaitong on the Pharmacokinetics of Losartan: An In Vivo UPLC-MSMS Study

Abstract EN

The aim of this study was to examine whether Xuesaitong, a multiherbal formulation for coronary heart disease, alters the pharmacokinetics of losartan.

Adult male Sprague Dawley rats randomly received losartan (10 mg/kg) or losartan plus Xuesaitong (10 mg/kg) through an oral gavage (n = 6).

Multiple blood samples were obtained for up to 36 h to determine the concentrations of losartan and its active metabolite, EXP3174, through ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).

Pharmacokinetics were estimated using a noncompartmental model.

The half-life (t1/2) of losartan was decreased by Xuesaitong (4.26 ± 1.51 vs.

6.35 ± 2.10 h; P<0.05).

The apparent volume of distribution (Vd) of losartan was also decreased by the combination of losartan and Xuesaitong (4.41 ± 1.61 vs.

7.20 ± 2.41 mL; P<0.05).

The time to maximum concentration (Tmax) of losartan was increased by Xuesaitong (1.06 ± 1.04 vs.

0.13 ± 0.05 h; P<0.05).

Xuesaitong also decreased the t1/2 of EXP3174 (8.22 ± 1.41 vs.

6.29 ± 1.38 h; P<0.05).

These results suggest that there is a complex interaction between losartan and Xuesaitong.

In addition to enhanced elimination of losartan and EXP3174, Xuesaitong may also decrease the absorption rate and Vd of losartan.