Effects of astragaloside IV on the pharmacokinetics of omeprazole in rats

Wei Liu,Guozhi Liu,Jing Liu

doi:10.1080/13880209.2019.1636828

Wei Liu, Guozhi Liu + Show 1 more

Open Access

https://doi.org/10.1080/13880209.2019.1636828

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Abstract

Context: Omeprazole and astragaloside IV (AS-IV) are widely used for the treatment of gastric ulcers in China clinics.Objective: This study investigates the effects of AS-IV on the pharmacokinetics of omeprazole in rats.Materials and methods: The pharmacokinetics of orally administered omeprazole (2 mg/kg), with or without AS-IV (100 mg/kg/day for 7 days) pretreatment, were investigated in male Sprague-Dawley rats (two groups of six animals each) using LC–MS/MS. A Caco-2 cell transwell model and rat liver microsome incubation systems were also used to support the in vivo pharmacokinetic data and investigate its potential mechanism.Results: The results indicated that co-administration of AS-IV could decrease the systemic exposure of omeprazole significantly (p < 0.05), including AUC0–t (717.20 ± 177.63 vs. 1166.25 ± 186.65 ng h/mL) and Cmax (272.35 ± 25.81 vs. 366.34 ± 32.57 ng/mL). The t1/2 of omeprazole also decreased significantly (1.78 ± 0.15 vs. 2.23 ± 0.27 h, p < 0.05). The efflux ratio of omeprazole across the Caco-2 cell transwell model increased significantly from 1.73 to 2.67 (p < 0.05), and the metabolic stability of omeprazole was decreased from 42.6 ± 7.8 to 26.2 ± 5.1 min with the pretreatment of AS-IV (p < 0.05).Discussion and conclusions: AS-IV could decrease the systemic exposure of omeprazole in rats when AS-IV and omeprazole were co-administered, and it might exert these effects through decreasing the absorption of omeprazole by inducing P-gp, or through accelerating the metabolism of omeprazole in rat liver by inducing the activity of CYP3A4.

Highlights

Omeprazole is an atypical proton pump inhibitor
Several research articles have indicated that Astragaloside IV (AS-IV) could modulate the activity of CYP3A4 and P-gp, which might lead to drug–drug interactions when they are co-administered with other herbs or drugs (Wang et al 2014; Zhang et al 2016)
Omeprazole and ASIV are widely used for the treatment of peptic ulcer in China clinics, and no reports were found on possible pharmacokinetic interactions between AS-IV and omeprazole, especially the effects of AS-IV on the pharmacokinetics of omeprazole

Summary

Introduction

Omeprazole is an atypical proton pump inhibitor. It is prescribed for the treatment of various acid-related diseases, such as peptic ulcer, gastroesophageal reflux diseases (Herrera-Mozo et al 2017; Selmi et al 2017; Talaat 2017; Yang et al 2017). Fang et al (2009) have reported that oral omeprazole undergoes marked extraction in the small intestine, and i.d. administration of ketoconazole and verapamil could increase the bioavailability of omeprazole through inhibiting the function of CYP3A4 and P-gp. Radix astragali [the root of Astragalus membranaceus (Fish) Bungevar. Several research articles have indicated that AS-IV could modulate the activity of CYP3A4 and P-gp, which might lead to drug–drug interactions when they are co-administered with other herbs or drugs (Wang et al 2014; Zhang et al 2016). Omeprazole and ASIV are widely used for the treatment of peptic ulcer in China clinics, and no reports were found on possible pharmacokinetic interactions between AS-IV and omeprazole, especially the effects of AS-IV on the pharmacokinetics of omeprazole

Objectives

Methods

Results