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Advances in study of metabolic activation of carboxyl-acid containing drugs by UGTs

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Author:: No author available

Journal Title:: ACTA PHARMACEUTICA SINICA

Issue:: 11

DOI:: 10.3321/j.issn:0513-4870.2009.11.002

Key Word:: 羧酸药物;葡萄糖醛酸转移酶;酰基葡萄糖醛酸苷;代谢激活;carboxyl-acid containing drug;uridine diphosphoglucuronosyl transferase;acyl glucuronide;metabolic activation

Abstract： The metabolic transformation of the drugs containing carboxylic acid groups can lead to the formation of acyl glucuronide metabolites through catalysis by glucuronosyltransferase, and produce pro-acyl glucuronide intermediate metabolites with electronic activity. Then, protein or DNA adducts appeared after a series of non-enzyme or enzyme reactions. These adducts would change the protein activity and potentially lead to idiosyncratic and genotoxicity. In this paper, we discussed the chemical activity, drug-induced mechanisms, distribution and toxicity resulting from this metabolic activation for these drugs, and stated the status and prospects of research in this field.

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