Two patients with COMT inhibitor-induced hepatic dysfunction and UGT1A9 genetic polymorphism

Neurology. 2005 Dec 13;65(11):1820-2. doi: 10.1212/01.wnl.0000187066.81162.70.

Abstract

The authors report two cases of catechol-O-methyltransferase (COMT) inhibitor-induced asymptomatic hepatic dysfunction in women with Parkinson disease. The patients were genotyped for the UDP-glucuronosyltransferase (UGT) 1A9 gene (which encodes the main COMT inhibitor-metabolizing enzyme), and found to carry mutations leading to defective glucuronidation activity. This suggests that UGT1A9 poor metabolizer genotype(s) may be a predisposing factor for COMT inhibitor-induced hepatotoxicity.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Aged
  • Antiparkinson Agents / adverse effects*
  • Benzophenones / adverse effects
  • Catechol O-Methyltransferase / metabolism
  • Catechol O-Methyltransferase Inhibitors*
  • Catechols / adverse effects
  • Chemical and Drug Induced Liver Injury*
  • DNA Mutational Analysis
  • Enzyme Inhibitors / adverse effects*
  • Enzyme Inhibitors / metabolism
  • Female
  • Genotype
  • Glucuronates / metabolism
  • Glucuronosyltransferase / genetics*
  • Humans
  • Liver / drug effects
  • Liver / enzymology
  • Liver / physiopathology
  • Liver Diseases / enzymology
  • Liver Diseases / genetics*
  • Middle Aged
  • Mutation / genetics
  • Nitriles
  • Nitrophenols / adverse effects
  • Parkinson Disease / drug therapy
  • Polymorphism, Genetic / genetics
  • Tolcapone
  • UDP-Glucuronosyltransferase 1A9

Substances

  • Antiparkinson Agents
  • Benzophenones
  • Catechol O-Methyltransferase Inhibitors
  • Catechols
  • Enzyme Inhibitors
  • Glucuronates
  • Nitriles
  • Nitrophenols
  • UGT1A9 protein, human
  • entacapone
  • Tolcapone
  • Catechol O-Methyltransferase
  • Glucuronosyltransferase
  • UDP-Glucuronosyltransferase 1A9