UDP-glucuronosyltransferases and clinical drug-drug interactions.
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Kiang TK, Ensom MH, Chang TK
UDP-glucuronosyltransferases and clinical drug-drug interactions.
Pharmacol Ther. 2005 Apr;106(1):97-132. Epub 2005 Jan 12.
- PubMed ID
- 15781124 [ View in PubMed]
- Abstract
UDP-glucuronosyltransferase (UGT) enzymes catalyze the conjugation of various endogenous substances (e.g., bilirubin) and exogenous compounds (e.g., drugs). The human UGT superfamily is comprised of 2 families (UGT1 and UGT2) and 3 subfamilies (UGT1A, UGT2A, and UGT2B). Many of the individual UGT enzymes are expressed not only in liver but also in extrahepatic tissues, where the extent of glucuronidation can be substantial. Several others (e.g., UGT1A7, UGT1A8, and UGT1A10) are expressed only in extrahepatic tissues. The molecular regulation of UGT enzyme is still not fully understood, but various transcription factors appear to play a regulatory role. The expression of individual UGT enzymes is subject to genetic polymorphism and these enzymes can be inhibited or induced by xenobiotics. Experimental evidence in humans indicates that the glucuronidation of acetaminophen, codeine, zidovudine, carbamazepine, lorazepam, and propafenone can influenced by specific interacting drugs. In contrast, the glucuronidation of diflunisal, morphine, naproxen, and temazepam is not affected appreciably by the drugs investigated to date. In general, UGT-mediated human drug interaction studies are difficult to interpret. The factors that complicate the interpretation of this type of drug interaction data are discussed.
DrugBank Data that Cites this Article
- Drugs
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Propacetamol UDP-glucuronosyltransferase 1-10 Protein Humans NoSubstrateDetails - Binding Properties
Drug Target Property Measurement pH Temperature (°C) Troglitazone UDP-glucuronosyltransferase 1-6 Ki (nM) 20000 N/A N/A Details Valproic acid UDP-glucuronosyltransferase 2B7 Ki (nM) 1600000 N/A N/A Details - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareAcetaminophenDiflunisal The serum concentration of Acetaminophen can be increased when it is combined with Diflunisal. ZidovudineAcetaminophen The metabolism of Zidovudine can be decreased when combined with Acetaminophen. ZidovudinePropacetamol The metabolism of Zidovudine can be decreased when combined with Propacetamol.