Effects of Herba Erigerontis injection on pharmacodynamics and pharmacokinetics of warfarin in rats in vivo.

Abstract

Herba Erigerontis injection (HEI) is an aqueous solution derived from whole plants of Erigeron breviscapus, which may be co-administered with warfarin to treat cardiovascular and cerebrovascular disorders. This research was conducted to make sure whether HEI would affect anticoagulation of warfarin to guarantee reasonable medication. The pharmacodynamic study was designed to measure prothrombin time (PT) and activated partial thromboplastin time (APTT) values, and international normalized ratio (INR) values were calculated. For pharmacokinetic study, ultra performance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS) technology was applied to measure plasma concentrations of warfarin enantiomers. The influence of HEI on plasma protein binding rate of warfarin was assessed by ultrafiltration. Pharmacodynamic study demonstrated that both HEI alone and co-administered with warfarin could increase PT and INR values significantly (P<.01), whereas the APTT values were unaffected (P>.05). Pharmacokinetic study manifested that Cmax , AUC and t1/2 prolonged significantly (P<.01) for R/S-warfarin in presence of HEI. Low (3.6mL/kg), medium (7.2mL/kg) and high (10.8mL/kg) doses of HEI could decrease plasma protein binding rate of warfarin significantly (P<.01). The results mean that HEI can potentiate the anticoagulant response of warfarin through both pharmacodynamics and pharmacokinetics.