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The Effect of Compound Danshen Dripping Pills on the Pharmacokinetics of Steady-state Warfarin in Rats

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【Author】 ZHANG Ling 1,2 ,CHU Yang2,WANG Xiang-yang2,GUO Jia-hua2,ZHAO Yong-yue2,LI Wei2,MA Xiao-hui2, GUO Zhi-xin 1,2 1.Tianjin University of Traditional Chinese Medicine,Tianjin 300193,China;2.Tasly R&D Institute,Tianjin Tasly Group Co.,Ltd.,Tianjin 300410,China

【摘要】 [Objective]To determine the potential interaction between the Chinese herb medicine,Compound Danshen Dripping Pills(CDDP)and a widely used oral anticoagulant warfarin in steady-state in vivo when administered concomitantly.[Method]Each day for 4 days the warfarin control group and the warfarin plus single-dose of CDDP group of rats were treated orally with warfarin(0.2 mg/kg,once per day at 8 a.m.),and the warfarin and CDDP combined treatment group of rats were treated orally with warfarin(0.2 mg/kg,once per day at 8 a.m.)and CDDP(500 mg/kg, once per day at 8 a.m.),the warfarin steady-state was achieved after 4 days of treatment,blood samples were collected each day(at 8 a.m.)for HPLC analysis.Until the 5 day the warfarin control group of rats were still treated orally with warfarin(0.2 mg/kg,once at 8 a.m.),the warfarin plus single-dose of CDDP group of rats were treated orally with warfarin(0.2 mg/kg,once at 8 a.m.)and CDDP(500 mg/kg,once at 8 a.m.), and the warfarin and CDDP combined treatment group of rats were still treated orally with warfarin(0.2 mg/kg,once at 8 a.m.)and CDDP(500 mg/kg,once at 8 a.m.),and blood samples were collected at 0,0.5,1,2,4,8,12,24,36,48 h after warfarin-treatment.The concentration of warfarin in blood plasma was determined by high performance liquid chromatography(HPLC).[Result]The linear calibration curve ranged from 0.05 to 10μg/ml,the limit of quantitation(LLOQ)for warfarin was 0.05 ng/ml(r>0.999),moreover,all the validation data including accuracy, precision(intra-and inter-day),sensitivity,recovery,stability,were within the required limits.CDDP did not alter the pharmacokinetic(PK)behavior of warfarin in steady-state in vivo in rats after simultaneous and concomitant treatment.[Conclusion]The simultaneous and concomitant treatment of rats with CDDP did not give rise to significant effects on the pharmacokinetics in steady-state of warfarin.

【基金】 Supported by National Key Special Project of Science and Technology for Innovation Drugs of China(Grant No.2008ZX09401-006)
  • 【分类号】R965
  • 【被引频次】1
  • 【下载频次】62
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