Measurement of the in Vitro Glucuronidation of Peroxisome Proliferator Carboxylic Acids by Liver Microsomes and Genetically Modified V79 Cell Line
Peroxisome proliferators (PP) belonging to the series of carboxylic acids are hypolipidemic drugs (clofibric acid, ciprofibrate, fenofibrate,...) or plastifiers (2-ethylhexanoic acid). In man, these substances are essentially excreted as acylglucuronides, which are formed by uridine-5’-diphosphate-(UDP)-glucuronosyltransferases (UGTs, EC 184.108.40.206), according to the following reaction: Open image in new window By contrast to ether glucuronides, ester (acyl) glucuronides are reactive metabolite species. At physiological pHs, they can undergo several non desirable reactions such as isomerization, hydrolysis, and transacylation, which can lead to the formation of covalently bound adducts with proteins . This has been proposed as the mechanism which causes immunological reaction in patients receiving certain carboxylic acid drugs, other than fibrates, which has led to such drugs being withdrawn from the market. They are therefore toxicologically relevant.
KeywordsHigh Performance Liquid Chromatography High Performance Liquid Chromatography High Performance Liquid Chromatography Analysis Peroxisome Proliferators Clofibric Acid
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