Alteration of the Efficacy and Toxicity of Clinically Useful Drug Esters by Organophosphate Inhibitors

摘要

The objectives of this project are to develop animal models to investigate the effects of organophosphate compounds on drug metabolism, especially the metabolism of therapeutically useful drugs which contain ester linkages with carboxylic acids. These drugs are metabolized by specific esterases (carboxylesterases) located mainly in the liver, lung and kidney. Inhibition of these enzymes would lead to either therapeutic failure (when ester hydrolysis is required for activation of the drug) or to drug toxicity (when ester hydrolysis is required for inactivation of the drug). Keywords: Carboxylesterase; Ester hydrolysis; Soman; Enzymes inhibition; Enzymes activation; Paraoxon; Efficacy; Toxicity; Organophosphates. (kt)