AUTHOR=Lv Chunxiao , Liu Changxiao , Yao Zhuhua , Gao Xiumei , Sun Lanjun , Liu Jia , Song Haibo , Li Ziqiang , Du Xi , Sun Jinxia , Li Yanfen , Ye Kui , Wang Ruihua , Huang Yuhong TITLE=The Clinical Pharmacokinetics and Pharmacodynamics of Warfarin When Combined with Compound Danshen: A Case Study for Combined Treatment of Coronary Heart Diseases with Atrial Fibrillation JOURNAL=Frontiers in Pharmacology VOLUME=8 YEAR=2017 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2017.00826 DOI=10.3389/fphar.2017.00826 ISSN=1663-9812 ABSTRACT=

Warfarin is used as anticoagulant and Compound Danshen prescription (CDP) is able to promote blood circulation. The combination might produce a synergic effect for patients of coronary heart diseases (CHDs) with atrial fibrillation (AF). Whether the combination increases the bleeding risk of warfarin is unclear, so the effects of Compound Danshen dripping pill (CDDP) on the pharmacokinetics (PK) and pharmacodynamics (PD) profiles of warfarin was investigated in patients. The dose and blood concentrations of warfarin, the four indicators of blood coagulation, prothrombin time, activated partial thromboplatin time, thrombin time, fibrinogen, and international normalized ratio value were compared when with and without CDDP treatment. The population PK (PPK) and PPK-PD models were established to assess patient demographics, genetic polymorphisms and CDDP as covariates. And the Seattle Angina Questionnaire was used to evaluate clinical efficacy, and the bleeding risk of combination was analyzed. The results indicated that CDDP had little influence on PK and PD profiles of warfarin in most patients and the combination of CCDP and warfarin would be a promising alternative regime for CHD with AF patients. The study was registered on China Clinical Trial Registry with number ChiCTR-ONRC-13003523.