Ticlopidine

Publication Title: 
The Journal of Pharmacology and Experimental Therapeutics

Aspirin (acetylsalicylic acid) and clopidogrel are two major antithrombogenic agents that are widely used for the treatment and prevention of cerebro- and cardiovascular conditions such as stroke. Combined use produces enhanced therapeutic effect. Aspirin and clopidogrel both are esters, and hydrolysis leads to decreased or inactivated therapeutic activity. The aim of the study was to determine whether aspirin and clopidogrel are hydrolyzed by the same enzyme(s), thus reciprocally prolonging the antithrombogenic activity.

Author(s): 
Tang, Man
Mukundan, Madhu
Yang, Jian
Charpentier, Nathan
LeCluyse, Edward L.
Black, Chris
Yang, Dongfang
Shi, Deshi
Yan, Bingfang
Publication Title: 
The Journal of Pharmacology and Experimental Therapeutics

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 the hydrolytic activation is catalyzed by carboxylesterase human carboxylesterase (HCE) 1. Liver microsomes rapidly hydrolyzed oseltamivir, but no hydrolysis was detected with intestinal microsomes or plasma.

Author(s): 
Shi, Deshi
Yang, Jian
Yang, Dongfang
LeCluyse, Edward L.
Black, Chris
You, Li
Akhlaghi, Fatemeh
Yan, Bingfang
Publication Title: 
Molecular Pharmacology

Carboxylesterases constitute a class of enzymes that play important roles in the hydrolytic metabolism of drugs and other xenobiotics. Patients with liver conditions such as cirrhosis show increased secretion of proinflammatory cytokines [e.g., interleukin-6 (IL-6)] and decreased capacity of hydrolysis. In this study, we provide a molecular explanation linking cytokine secretion directly to the decreased capacity of hydrolytic biotransformation.

Author(s): 
Yang, Jian
Shi, Deshi
Yang, Dongfang
Song, Xiulong
Yan, Bingfang
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