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 ultraperfonnance 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.
[1]Shanghai Univ Med & Hlth Sci, Jiading Dist Cent Hosp, Dept Pharm, Shanghai, Peoples R China.
[2]Shanghai Eastern Hepatobiliary Surg Hosp, Shanghai, Peoples R China.
[3]Shanghai Univ Med & Hlth Sci, Jiading Dist Cent Hosp, Dept Thorac Surg, Shanghai, Peoples R China.
[4]Shanghai Univ TCM, Yueyang Hosp Integrated Tradit Chinese Med & West, Dept Pharm, Shanghai, Peoples R China.
[5]Shanghai Baoshan Luodian Hosp, Dept Pharm, Shanghai, Peoples R China.
(8.0+极速模式)