Nutt J G, Woodward W R, Beckner R M, Stone C K, Berggren K, Carter J H, Gancher S T, Hammerstad J P, Gordin A
Department of Neurology, School of Medicine, Oregon Health Sciences University, Portland 97201-3098.
Neurology. 1994 May;44(5):913-9. doi: 10.1212/wnl.44.5.913.
Catechol-O-methyltransferase (COMT) metabolizes a portion of administered levodopa and thus makes it unavailable for conversion to dopamine in the brain. In an open-label trail, we examined the effects of entacapone, a peripheral inhibitor of COMT, administered acutely or for 8 weeks, on the pharmacokinetics and pharmacodynamics of levodopa in 15 parkinsonian subjects with a fluctuating response to levodopa. Acutely and chronically administered entacapone similarly decreased the plasma elimination of orally and intravenously administered levodopa. Absorption of levodopa was minimally affected. During chronic entacapone treatment, daily levodopa dosages were reduced by 27% yet mean plasma levodopa concentrations were increased by 23%. Plasma 3-O-methyldopa concentrations were decreased by 60%. Entacapone increased the duration of action of single doses of levodopa by a mean of 56%. The percent of the day "on" after 8 weeks of entacapone treatment was 77%; it dropped to 44% upon withdrawal of entacapone. We conclude that inhibition of COMT by entacapone increases the plasma half-life of levodopa and augments the antiparkinsonian effects of single and repeated doses of levodopa.
儿茶酚-O-甲基转移酶（COMT）可代谢一部分外源性左旋多巴，从而使其无法在脑内转化为多巴胺。在一项开放标签试验中，我们研究了外周COMT抑制剂恩他卡朋急性给药或给药8周对15例对左旋多巴反应波动的帕金森病患者左旋多巴药代动力学和药效学的影响。急性和长期给予恩他卡朋同样降低了口服和静脉注射左旋多巴的血浆清除率。左旋多巴的吸收受到的影响最小。在恩他卡朋长期治疗期间，左旋多巴的每日剂量减少了27%，但左旋多巴的平均血浆浓度却升高了23%。血浆3-O-甲基多巴浓度降低了60%。恩他卡朋使单剂量左旋多巴的作用持续时间平均延长了56%。恩他卡朋治疗8周后“开”期的百分比为77%；停用恩他卡朋后降至44%。我们得出结论，恩他卡朋抑制COMT可增加左旋多巴的血浆半衰期，并增强单剂量和重复剂量左旋多巴的抗帕金森病作用。
