Investigating the Herb-Drug Interaction Between Danhong Injection and Dapagliflozin in Rats

Background and Objective: Danhong injection (DHI) and Dapagliflozin (DAPA) cured diabetes and coronary heart disease and metabolized via the liver. The study observed the possible interaction of DHI and DAPA in vivo. Materials and Methods: The rats were divided into six groups: DAPA alone and co-administered with low/high-dose DHI for 7 days and DHI alone and co-administered with low/high-dose DAPA. The blood samples were collected at different times. The plasma concentrations of DAPA and salvianolic acid B (SAB), an ingredient in DHI, were analyzed. The rat liver microsomes (RLMs) investigate the UGT1A9 activity and protein concentration in the metabolism of DAPA and DHI. Results: The major PKs of DAPA, including AUC((0-t)), CLz/F, Vz/F and T-max, were significantly influenced by co-administration DHI. Conversely, the primary PKs of SAB, including AUC((0-t)), AUC((0-)(infinity)), T-max, CLz/F, Vz/F and C-max, were remarkable differences between DHI alone and co-administration DAPA. In the RLMs, low-dose DHI was a significant inhibitor of DAPA in UGT1A9 activity. There were no apparent changes in the protein concentration with RLMs in groups. Conclusion: The findings elucidated that there were partial differences in PK properties of DHI and SAB among groups, with a slight influence on the UGT1A9 activity. Increasing the amount of DHI resulted in a weakening of the effect of DAPA. The SAB changes may be induced by compounds of DHI with CYP-related and self-metabolism.