warfarin and tanshinone

This study was to explore the effects of sulfotanshinone sodium injection (SSI) on the pharmacokinetics and pharmacodynamics of warfarin in rats.The studies of single dose and multiple dose of warfarin were designed to assess the interaction between warfarin and SSI. Rats were divided into different groups randomly and administered with warfarin in the absence or presence of SSI. Prothrombin time (PT) and activated partial thromboplastin time (APTT) values were detected by blood coagulation analyzer, and international normalized ratio (INR) values were calculated. Plasma concentrations of warfarin enantiomers were determined by UPLC-MS/MS method, pharmacokinetic parameters were calculated.The single-dose study demonstrated that the repeated doses of SSI alone had no effect on PT, APTT and INR values, but had a significant effect on PT and INR values produced by a single dose of warfarin, APTT values were unaffected. The

Topics: Abietanes; Animals; Chromatography, Liquid; Humans; International Normalized Ratio; Male; Partial Thromboplastin Time; Prothrombin Time; Rats; Tandem Mass Spectrometry; Warfarin

Enhanced anticoagulation and/or even bleeding are often observed when patients on long-term warfarin (WAR) therapy consumed Danshen, a well-known medicinal herb in traditional Chinese medicine (TCM). This study demonstrates that altered WAR metabolism, arising from its interaction with the active components in Danshen, played a significant role in this curative effect. Mass spectrometric techniques including ESI-ITMS (electrospray ionization ion-trap mass spectrometry) and ESI-TOF (time-of-flight)-MS have been developed for the study of such drug-herb interactions. The experimental approach involved a detailed analysis and comparison of WAR metabolites in vivo from blood or urine of rats that had been orally administrated with WAR, either singly or together with the representative bioactive component of Danshen-lipid soluble TIIA (Tanshinon IIA), and a study of the interaction of human serum albumin (HSA), WAR, and water-soluble sodium tanshinone IIA sulfonate (STS) in vitro. Results demonstrate that TIIA accelerates the metabolic rate of WAR, whereas STS displaces WAR from the WAR-HSA complex, resulting in an increase of free WAR concentration in blood. It is suggested that the elevated level and enhanced metabolism of WAR is responsible for the over-anticoagulation effect observed.

Topics: Abietanes; Animals; Binding, Competitive; Drugs, Chinese Herbal; Herb-Drug Interactions; Humans; Male; Phenanthrenes; Protein Binding; Rats; Rats, Sprague-Dawley; Serum Albumin; Spectrometry, Mass, Electrospray Ionization; Warfarin