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

Objective: This study aimed to investigate effect of antidiabetic herb Astragali Radix (AR) on pharmacokinetic behavior of dapagliflozin (DAPA) in healthy rats and type 2 diabetes mellitus (T2DM) rats. Methods: 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. Results: The diabetes status and co-administrated with ARE significantly affected pharmacokinetic behaviors of DAPA in the rats. Compared to that in healthy rats, t max of DAPA significantly shortened, its C max significantly increased in T2DM rats, and its t 1/2 , V , AUC, CL and MRT kept unchanged. When ARE was co-administrated with DAPA, C max of DAPA significantly increased, its t max and MRT significantly decreased, and its t 1/2 , V , AUC and CL kept unchanged in healthy rats. t max and C max of DAPA significantly decreased, its t 1/2 and V 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 in vivo . Conclusion: Both disease status of T2DM and co-administration of ARE affect pharmacokinetic behavior of DAPA in vivo . Potential pharmacokinetic interactions may occur in vivo when herbs and drugs are co-administrated, which may affect efficacy and safety of drugs.