Altered Therapeutic Window of Coronary Heart Disease Treatment Drug Clopidogrel in Drug-Induced Cholestasis Patients

作者：Zhao, Bo; Peng, Jian-Jun^*; Ren, Li-Hui; Wang, Zuo-Yan; Lei, Li-Cheng; Ye, Hui-Ming; Zhao, Sheng

来源：Latin American Journal of Pharmacy, 2016, 35: 1269-1272.

• bile acids
• clopidogrel
• cholestasis
• hydrolysis

Clopidogrel is an important clinical drug used to treat coronary heart disease, and its therapeutic window might be changed in patients with liver diseases. Drug-induced cholestasis remains to be a major adverse effect to limit the clinical application of many drugs. Alpha-naphthylisothiocyanate (AN-IT)-induced liver injury and intrahepatic cholestasis was used model drug-induced cholestasis in human. The results showed that oral gavage of 75 mg/kg for 2 days significantly increased the activity of ALT and AST. Metabolomics study showed the alteration of levels of bile acids, including significantly elevated level of CA. In vitro inhibition evaluation experiment was performed to determine the inhibition of bile acids towards human esterase-catalyzed metabolism of clopidogrel, trying to indicate the influence of bile acids towards the therapeutic window of clopidogrel. The results showed that CA inhibited the metabolism of clopidogrel. In conclusion, the present study demonstrated the altered therapeutic window of coronary heart disease treatment drug clopidogrel in drug-induced cholestasis patients, guiding the clinical application of coronary heart disease treatment drugs.

• 出版日期2016
• 单位首都医科大学