Pharmacogenetics of Uridine Diphosphoglucuronosyltransferase (UGT) 1A Family Members and its Role in Patient Response to Irinotecan
- 1 January 2006
- journal article
- review article
- Published by Taylor & Francis in Drug Metabolism Reviews
- Vol. 38 (3) , 393-409
- https://doi.org/10.1080/03602530600739835
Abstract
Glucuronidation, catalyzed by the glucuronosyltransferase (UGT) superfamily, is a major biotransformation pathway for several drugs, including irinotecan. Irinotecan is commonly used in colorectal cancer chemotherapy. Irinotecan undergoes metabolism in humans and is converted to its active metabolite SN-38, a topoisomerase I inhibitor. SN-38 is inactivated via glucuronidation catalyzed by various hepatic and extrahepatic UGT1A isozymes. Although the role of the UGT1A1 *28 genetic variant has received much attention in altered toxicity upon irinotecan treatment, other UGT1A enzymes also play an important role. This review summarizes pharmacokinetic, toxicologic, and pharmacogenetic studies carried out to date in irinotecan and SN-38 disposition.Keywords
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