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Effects of Cucurbitacin E, a Tetracyclic Triterpene Compound from Cucurbitaceae , on the Pharmacokinetics and Pharmacodynamics of Warfarin in Rats
Author(s) -
Ding Tonggui,
Zhang Yuanjin,
Chen Ang,
Tang Yu,
Liu Mingyao,
Wang Xin
Publication year - 2015
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.12329
Subject(s) - pharmacokinetics , warfarin , pharmacology , prothrombin time , pharmacodynamics , chemistry , triterpene , partial thromboplastin time , cucurbitaceae , medicine , platelet , biology , atrial fibrillation , botany , alternative medicine , pathology
This study firstly investigated the effects of cucurbitacin E (CuE), a tetracyclic triterpene compound from Cucurbitaceae , on the pharmacokinetics ( PK ) and pharmacodynamics ( PD ) of warfarin, a model CYP 2C probe substrate, in the rat. In PK studies, the concentration of warfarin in blood samples was determined by HPLC ‐ DAD , and the PK parameters were analysed using non‐compartmental methods. In PD studies, the prothrombin time ( PT ) in blood plasma at each sample point was measured via thromboplastin reagents. CuE treatment (50, 100 and 200 μg/kg, i.p.) decreased warfarin clearance (28–32%), increased the area under the curve ( AUC 0–∞ ; 55–62%) and prolonged plasma half‐life ( t 1/2 ; 58–72%). At the same time, the anticoagulation effect of warfarin ( PT max ) was also significantly increased in the presence of CuE. These data demonstrated that CuE affected the PK and PD of warfarin, and these effects may be due to the inhibition of CYP 2C activity by CuE. Hence, careful monitoring should be carried out during concomitant use of herbal products containing CuE with drugs that are metabolized by CYP 2C enzymes.