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

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 (t(1/2)) of losartan was decreased by Xuesaitong (4.26 ± 1.51 vs. 6.35 ± 2.10 h; P < 0.05). The apparent volume of distribution (V(d)) 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 (T(max)) of losartan was increased by Xuesaitong (1.06 ± 1.04 vs. 0.13 ± 0.05 h; P < 0.05). Xuesaitong also decreased the t(1/2) 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 V(d) of losartan.