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

Weina Ma,Liang Zhao,Hua Nian,Lei Lv,Jungang Guo,Yongjun Meng,Xiaoliang Yang,Lijun Zhu,Yinghua Wang

doi:10.1155/2019/8373476

Abstract

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.

Highlights

Xuesaitong is a traditional Chinese medicine with multiple pharmacological activities
We examined the impact of Xuesaitong on the pharmacokinetic profile of losartan upon oral administration in rats
Calibration curves for losartan and EXP3174 comprised plots of the peak-area ratio of the analyte to internal standard (IS) against plasma concentration with a 1/x weighting

Summary

Introduction

Xuesaitong is a traditional Chinese medicine with multiple pharmacological activities. Major components of Xuesaitong are saponins from Panax notoginseng (PNS), including ginsenoside Rb1, ginsenoside Rg1, and notoginsenoside R1 [1]. Many patients receiving angiotensin-II-receptor antagonists for hypertension receive Xuesaitong [6,7,8]. As a nonpeptide angiotensin-II-receptor antagonist, losartan is the first of its kind in the market [9,10,11]. Losartan is metabolized into EXP3174—which is an active carboxylic-acid metabolite—by the cytochrome P450 subtypes, CYP3A4 and CYP2C9 [12, 13]. E elimination of EXP3174 requires cytochromes CYP3A4 and CYP2C9 [12]. EXP3174 has a much higher affinity for the angiotensin-II receptor and is mostly responsible for losartan’s pharmacodynamic properties [14]

Methods

Results

Discussion

Conclusion