Effect of Danhong injection on pharmacokinetics and pharmacodynamics of rivaroxaban in rats

Background and objectives Rivaroxaban is often used in combination with DHI to treat thromboembolic disease. Whether the combination causing HDIs is still unknown. The purpose of this study was to evaluate effects of DHI on pharmacokinetics and pharmacodynamics of rivaroxaban in rats and effects on CYP3A2. Methods Plasma concentration of rivaroxaban with or without DHI was determined by HPLC. Pharmacokinetics parameters were calculated. Effect of DHI on pharmacodynamics of rivaroxaban was investigated by APTT, PT, TT, FIB, INR, length of tail thrombosis, vWF, t-PA, PAI-1, IL-1 beta, TNF-alpha and histopathological sections. Effect of DHI on CYP3A2 in rats was investigated by probe drug method. Results C-max and AUC of rivaroxaban increased significantly in combination group (P < 0.05). APTT, PT, INR and TT increased (P < 0.05), length of tail thrombosis, FIB, vWF, PAI-1, IL-1 beta and TNF-alpha of combination group decreased significantly (P < 0.05) compared with rivaroxaban or DHI alone. Histopathologic section of tail thrombus had significant improvement. C-max and AUC of dapsone increased (P < 0.05) in DHI group. Conclusion In summary, DHI is an inhibitor of CYP3A2 and could significantly affect pharmacokinetics and pharmacodynamic of rivaroxaban, enhance anticoagulant and antithrombotic efficacy in rats. However, the combination of rivaroxaban and DHI might lead to potential HDIs. The dosage of rivaroxaban should be adjusted in clinical.