Hepatotoxic profile of catechol-O-methyltransferase inhibitors in Parkinson's disease.
Entacapone and tolcapone are selective catechol-O-methyltransferase (COMT) inhibitors developed recently as adjuncts to levodopa for the treatment of Parkinson's disease (PD). They extend the duration of action of levodopa. As a result, they increase 'on' time, decrease 'off' time and improve motor scores in patients with motor fluctuations. Both benefits and main side effects are related to increased dopaminergic activity. This paper reviews the use of those COMT inhibitors in PD with particular focus on the issue of hepatotoxicity. Neither tolcapone nor entacapone caused hepatotoxicity in preclinical studies. However, in 1998, four patients who were using tolcapone presented with serious liver dysfunction; three of them died due to acute liver failure. Tolcapone is now known to have the potential to cause hepatotoxicity in clinical use and experimental studies. It is now recommended that tolcapone be administered only in patients with motor fluctuations who are no longer satisfactorily treated with other medications for PD. Routine liver monitoring is now mandatory with this agent. Entacapone has been described as a well-tolerated and safe drug in recent experimental studies, human clinical trials and postmarketing surveillance. It can be offered to any patient with motor fluctuations and routine liver monitoring is not required.
Benabou
Reina
R
The Center for Parkinson's Disease and Other Movement Disorders, New York-Presbyterian Hospital, Columbia Presbyterian Medical Center, The Neurological Institute, 710 West 168th Street, Room 350, New York, NY 10032, USA. RBenabou@neuro.columbia.edu
Waters
Cheryl
C
D000978:Antiparkinson Agents / Q000493:pharmacokinetics; D001577:Benzophenones / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology*; D056487:Chemical and Drug Induced Liver Injury, Chronic / Q000209:etiology; D004791:Enzyme Inhibitors / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D007980:Levodopa / Q000493:pharmacokinetics; D009570:Nitriles; D009596:Nitrophenols; D010300:Parkinson Disease / Q000188:drug therapy* / Q000201:enzymology; D000077867:Tolcapone
D000978:Antiparkinson Agents; D001577:Benzophenones; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols; D004791:Enzyme Inhibitors; D009570:Nitriles; D009596:Nitrophenols; D007980:Levodopa; C071192:entacapone; D000077867:Tolcapone