AUTHOR=Du Wandi , Hu Jiarong , Liang Jingru , Yang Xiaolei , Fang Boyu , Ma Guo 

TITLE=Effect of Astragali radix extract on pharmacokinetic behavior of dapagliflozin in healthy and type 2 diabetic rats

JOURNAL=Frontiers in Pharmacology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1214658

DOI=10.3389/fphar.2023.1214658

ISSN=1663-9812

ABSTRACT=<p><bold>Objective:</bold> This study aimed to investigate effect of antidiabetic herb <italic>Astragali Radix</italic> (AR) on pharmacokinetic behavior of dapagliflozin (DAPA) in healthy rats and type 2 diabetes mellitus (T2DM) rats.</p><p><bold>Methods:</bold> The T2DM rats were induced by high-fat diet (HFD) and intraperitoneal injection of streptozotocin (STZ). Concentrations of DAPA in healthy and T2DM rat plasma were determined by UPLC-MS/MS method. Effect of AR extract (ARE) on pharmacokinetic behavior of DAPA in healthy and T2DM rats was evaluated, respectively.</p><p><bold>Results:</bold> The diabetes status and co-administrated with ARE significantly affected pharmacokinetic behaviors of DAPA in the rats. Compared to that in healthy rats, <italic>t</italic><sub>max</sub> of DAPA significantly shortened, its <italic>C</italic><sub>max</sub> significantly increased in T2DM rats, and its <italic>t</italic><sub>1/2</sub>, <italic>V</italic>, AUC, CL and MRT kept unchanged. When ARE was co-administrated with DAPA, <italic>C</italic><sub>max</sub> of DAPA significantly increased, its <italic>t</italic><sub>max</sub> and MRT significantly decreased, and its <italic>t</italic><sub>1/2</sub>, <italic>V</italic>, AUC and CL kept unchanged in healthy rats. <italic>t</italic><sub>max</sub> and <italic>C</italic><sub>max</sub> of DAPA significantly decreased, its <italic>t</italic><sub>1/2</sub> and <italic>V</italic> significantly increased, and its AUC, CL and MRT were unchanged in T2DM rats when ARE was co-administrated with DAPA. Co-administration of DAPA and ARE promoted absorptive rate of DAPA, increased its extravascular tissue distribution, and prolonged its duration of action. ARE did not cause accumulation of DAPA <italic>in vivo</italic>.</p><p><bold>Conclusion:</bold> Both disease status of T2DM and co-administration of ARE affect pharmacokinetic behavior of DAPA <italic>in vivo</italic>. Potential pharmacokinetic interactions may occur <italic>in vivo</italic> when herbs and drugs are co-administrated, which may affect efficacy and safety of drugs.</p>