UDP-glucuronosyltransferase 1A1
Also known as: UGT1A1, UGT1
Enzyme of the UDP-glucuronosyltransferase complex (family 1A) that catalyses glucuronidation of drugs and endogenous metabolites (bilirubin, morphine, paracetamol, NSAIDs). It is mainly expressed in the liver.
UGT1A1 inhibition (e.g. valproate, fluconazole) may increase toxicity of drugs metabolised by glucuronidation; genetic deficiency (Gilbert syndrome) affects irinotecan and bilirubin elimination.
Substrates: morphine (→ morphine-6-glucuronide), paracetamol (via glucuronidation), bilirubin, paradecam, NSAIDs (ibuprofen, diclofenac).
Inhibitors: valproate, fluconazole, fluoxetine, probenecid, valproic acid.
Inducers: rifampicin, carbamazepine, phenytoin (UGT1A1 induction via PXR/CAR).
UGT1A1 deficiency (Gilbert) is common (5-10% of the population) and increases irinotecan toxicity; valproate may raise morphine concentrations by inhibiting glucuronidation.
DailyMed/FDA (NIH/NLM) — approved labels (morphine, paracetamol, valproate); PubMed (NIH/NLM) — UGT1A1 pharmacology
