Benabou Reina, Waters Cheryl
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.
Expert Opin Drug Saf. 2003 May;2(3):263-7. doi: 10.1517/14740338.2.3.263.
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.
恩他卡朋和托卡朋是最近开发的选择性儿茶酚-O-甲基转移酶（COMT）抑制剂，作为左旋多巴的辅助药物用于治疗帕金森病（PD）。它们延长了左旋多巴的作用时间。因此，它们增加了“开”期时间，减少了“关”期时间，并改善了有运动波动的患者的运动评分。其益处和主要副作用均与多巴胺能活性增加有关。本文综述了这些COMT抑制剂在帕金森病中的应用，特别关注肝毒性问题。在临床前研究中，托卡朋和恩他卡朋均未引起肝毒性。然而，1998年，四名使用托卡朋的患者出现了严重的肝功能障碍；其中三人因急性肝衰竭死亡。现在已知托卡朋在临床应用和实验研究中具有引起肝毒性的可能性。现在建议仅在那些对帕金森病的其他药物治疗不再满意的有运动波动的患者中使用托卡朋。使用这种药物时现在必须进行常规肝脏监测。在最近的实验研究、人体临床试验和上市后监测中，恩他卡朋被描述为一种耐受性良好且安全的药物。它可以用于任何有运动波动的患者，并且不需要进行常规肝脏监测。
