Drug glucuronidation in humans

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Abstract

Glucuronidation is a major metabolic pathway for a large number of drugs in humans. Conjugation of drugs and other chemicals with glucuronic acid is catalyzed by the multigene UDP-glucuronosyltransferase family. It is believed that a number (unspecified at present) of glucuronosyltransferase isozymes, which probably differ in terms of substrate specificity and regulation, contribute to drug glucuronidation. Factors known to influence the pharmacokinetics of glucuronidated drugs in man, presumably via an effect on specific glucuronosyltransferases, include age (especially the neonatal period), cigarette smoking, diet, certain disease states, coadministered drugs, ethnicity, genetics and hormonal effects.

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      Given the scope of the glucuronidation reaction, it is not surprising that conjugation with glucuronic acid plays an important role in the metabolism of a myriad of compounds. In particular, glucuronidation is an elimination pathway for drugs from almost all therapeutic classes (Kiang, Ensom, & Chang, 2005; Miners & Mackenzie, 1991; Miners, Mackenzie, & Knights, 2010; Stingl, Bartels, Viviani, Lehmann, & Brockmoller, 2014). Evans and Relling (1999) estimated that glucuronidation was the primary route of metabolism for approximately 40% of drugs eliminated by conjugation enzymes, while an analysis of the 200 top-prescribed drugs in 2002 demonstrated that glucuronidation was the second most common metabolic pathway after cytochrome P450 (CYP) catalysed oxidation (Evans & Relling, 1999; Williams et al., 2004).

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