The effect of Compound Danshen Dripping Pills, a Chinese herb medicine, on the pharmacokinetics and pharmacodynamics of warfarin in rats

Aim of the study: Significant pharmacokinetic/pharmacodynamic (PK/PD) interactions between various herbal products and warfarin have recently been reported. The present study was conducted to determine whether Compound Danshen Dripping Pills (CDDP), a Chinese herb medicine used for the treatment of cardiovascular diseases, interacts with warfarin when administered concomitantly. Materials and methods: Each day for 7 days two groups of rats were treated orally with CDDP (50 mg/kg and 250 mg/kg, twice daily), and the control group received similar treatment with appropriate volumes of water only. Sixty minutes after the final daily administration of CDDP or water, an aqueous solution of warfarin (0.2 mg/mL) was given to each rat at a dose of 1.0 mg/kg, and blood samples were collected at 0, 0.5, 1, 2, 4, 8, 12, 24, 36, and 48 h after warfarin-treatment. The concentration of warfarin in blood plasma was determined by high performance liquid chromatography (HPLC). Prothrombin time (PT) in blood plasma was measured using thromboplastin reagent. Results: Excellent linearity was found between 0.05 and 10 mu g/mL with a lower limit of quantitation (LLOQ) of 0.05 ng/mL (r > 0.999); moreover, all the validation data including accuracy and precision (intra- and inter-day), were within the required limits. No significant differences were found in PT(max) and AUC(PT 0-infinity) between the two CDDP-treated groups and the control. Besides, there was little alteration in any of the pharmacokinetic parameters of warfarin between the two CDDP-treated groups and the control. Conclusion: The concomitant application of CDDP and warfarin did not give rise to significant effect on the pharmacodynamics of warfarin, and practically no effect on its pharmacokinetics. It was speculated that the PK/PD interactions between CDDP and warfarin was likely to be negligible as long as the patients took CDDP at a normal dose. (C) 2011 Elsevier Ireland Ltd. All rights reserved.