A Commonly Used Chinese Herbal Formula Shu-Jing-Hwo-Shiee-Tang Potentiates Anticoagulant Activity of Warfarin in a Rabbit Model

摘要

Background: Drug interactions between traditional Chinese herbal medicines and the anticoagulant warfarin may cause patient harm and are, therefore, important in clinical practice. Our experience in daily practice suggests that prothrombin time (PT) is prolonged when warfarin is used in combination with the Chinese herbal formula Shu-Jing-Hwo-Shiee-Tang (SJHST) commonly used by patients with osteoarthritis. Objective: We conducted animal experiments to confirm the effect of SJHST and warfarin on anticoagulant activity. Methods: Forty-eight male New Zealand white rabbits were randomized into eight groups of six rabbits. Group A (Control group) was administered normal saline. Group B (Western Medicine group) was administered warfarin 1.5 mg/kg/day. Groups C, D, and E [Traditional Chinese Medicine (TCM) groups] were administered different doses of SJHST (0.5 mg/kg/day, 1 mg/kg/day, and 2 mg/kg/day, respectively). Groups F, G, and H (Combination Therapy groups) were administered warfarin 1.5 mg/kg/day and different doses of SJHST (0.5 mg/kg/day, 1 mg/kg/day, and 2 mg/kg/day, respectively). The total duration of treatment was 14 days. Blood samples were obtained prior to beginning the experiments (day 0) and on day 7, day 14, and day 17 (3 days after discontinuation of the medications). The activated partial thromboplastin time (APTT), PT, and thrombin time (TT) were calculated and compared among the different groups. Results: No significant changes were noted in APTT, PT or TT between the control and SJHST-only groups. Significant prolongations of APTT and PTT, but not TT, were observed in the combination groups compared to the warfarin-only group. The enhanced anticoagulant effects returned to normal three days after discontinuation of SJHST treatment. Conclusions: We confirmed that the Chinese herb SJHST enhances the anticoagulant effect of warfarin. Although the exact mechanisms of the interaction are unknown, physicians should be aware of the possibility of drug interactions between warfarin and Chinese herbal medicines owing to the increased risk of bleeding.