Anti-Influenza Prodrug Oseltamivir Is Activated by Carboxylesterase Human Carboxylesterase 1, and the Activation Is Inhibited by Antiplatelet Agent Clopidogrel

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 319; no. 3; pp. 1477 - 1484
• Main Authors: Shi, Deshi, Yang, Jian, Yang, Dongfang, LeCluyse, Edward L., Black, Chris, You, Li, Akhlaghi, Fatemeh, Yan, Bingfang
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2006; American Society for Pharmacology and Experimental Therapeutics
• Subjects: Antiviral Agents - metabolism; Carboxylic Ester Hydrolases - antagonists & inhibitors; Carboxylic Ester Hydrolases - metabolism; Cell Line; Cell Survival - drug effects; Clopidogrel; Drug Interactions; Humans; Hydrolysis; Mass Spectrometry; Microsomes - drug effects; Microsomes - metabolism; Mutagenesis, Site-Directed; Oseltamivir - metabolism; Platelet Aggregation Inhibitors - pharmacology; Ticlopidine - analogs & derivatives; Ticlopidine - pharmacology; Transfection

Oseltamivir is the main medicine recommended by the World Health Organization in anticipation of next influenza pandemic. This anti-influenza viral agent is an ester prodrug, and the antiviral activity is achieved by its hydrolytic metabolite: oseltamivir carboxylate. In this study, we report that t...