UDP-glucuronosyltransferases and clinical drug-drug interactions.

Article Details

Citation

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
DrugEnzymeKindOrganismPharmacological ActionActions
PropacetamolUDP-glucuronosyltransferase 1-10ProteinHumans
No
Substrate
Details
Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
TroglitazoneUDP-glucuronosyltransferase 1-6Ki (nM)20000N/AN/ADetails
Valproic acidUDP-glucuronosyltransferase 2B7Ki (nM)1600000N/AN/ADetails
Drug Interactions
DrugsInteraction
Acetaminophen
Diflunisal
The serum concentration of Acetaminophen can be increased when it is combined with Diflunisal.
Zidovudine
Acetaminophen
The metabolism of Zidovudine can be decreased when combined with Acetaminophen.
Zidovudine
Propacetamol
The metabolism of Zidovudine can be decreased when combined with Propacetamol.