Pharmacokinetic and pharmacodynamic interaction of Danshen–Gegen extract with warfarin and aspirin

Danshen–Gegen (DG) product has clinically been proven to be an effective agent for heart-tonic efficacy by our previous research. In the mean time, herb–drug interactions between DG product and its commonly co-administered drugs, such as aspirin or warfarin need to be explored to ensure its safe clinical usage. Current study aims to investigate whether DG extract interacts with warfarin or aspirin when administered concomitantly to ensure the safety and efficacy of their usage. Five groups of SD rats (n=6/group) received DG alone (0.15 g/kg, human relevant dose), warfarin alone (0.2 mg/kg), warfarin (0.2 mg/kg) in combination with DG (0.15 g/kg), aspirin alone (10.3 mg/kg), or aspirin (10.3 mg/kg) in combination with DG (0.15 g/kg), respectively. DG product was given twice daily for 5 day. Warfain or aspirin were given once daily for 5 day. DG morning doses were given 2 h post that of warfarin/aspirin. Following first dosing on day 5, plasma samples were collected at different time points. For the pharmacodynamic measurement, whole blood was collected at 30 min after DG dosing or at 2.5 h after warfarin/aspirin dosing, and the prothrombin time assay was conducted. Co-administration of DG with warfarin could significantly decrease the Cmax, AUC and the prothrombin time of warfarin (p<0.05). In the mean time, the Cmax and AUC of danshensu, the active bioavailable component of DG were significantly increased (p<0.01) in presence of warfarin. Co-administration of DG with aspirin could significantly increase the Cmax and AUC of both aspirin (p<0.01) and its metabolite salicylic acid (p<0.01) and significantly decrease the prothrombin time of aspirin (p<0.05). However, the pharmacokinetics parameters of danshensu were not significantly affected by aspirin. Our animal study indicated that co-administration of DG with warfarin/aspirin can cause significant pharmacokinetic and pharmacodynamic herb–drug interactions in rat.