Kaakkola S, Teräväinen H, Ahtila S, Rita H, Gordin A
Department of Neurology, University of Helsinki, Finland.
Neurology. 1994 Jan;44(1):77-80. doi: 10.1212/wnl.44.1.77.
We studied the effect of entacapone, a selective catechol-O-methyltransferase inhibitor, on the bioavailability and clinical effect of levodopa in Parkinson's disease (PD). On day 1 (control day), nine patients received their own levodopa (plus benserazide) medication only; for the next 7 days they received 200 mg of entacapone with each dose of levodopa (tid or qid). We evaluated disability in the morning (8 AM) before drug administration and then at 1-hour intervals until 6 PM on days 1, 2, and 8, using a modified motor part of the Unified Parkinson's Disease Rating Scale. Repeated blood samples were taken before and during the 4 hours after the morning drugs for pharmacokinetic evaluation of entacapone and of levodopa and its metabolites. Added to the levodopa treatment, entacapone decreased clinical disability by about 16% (p < 0.05) from day 1 to day 8. The area under the curve (AUC) of levodopa increased by 38% (p < 0.01) after administration of a single dose of entacapone and by 40% (p < 0.05) after 7 days of multiple dosing with entacapone. Entacapone did not change the Tmax and Cmax values of levodopa. After 7 days of treatment with entacapone, the AUC of 3-O-methyldopa had decreased by 44% (p < 0.01) and of homovanillic acid by 26% (p < 0.05) as compared with treatment with levodopa alone. Four patients became slightly more dyskinetic during entacapone treatment than before it. The combination of entacapone and levodopa was well tolerated, judged by the lack of significant changes in hemodynamic and safety variables.(ABSTRACT TRUNCATED AT 250 WORDS)
我们研究了选择性儿茶酚-O-甲基转移酶抑制剂恩他卡朋对帕金森病（PD）患者左旋多巴生物利用度及临床疗效的影响。第1天（对照日），9例患者仅服用其自身的左旋多巴（加苄丝肼）药物；接下来7天，他们每次服用左旋多巴时均加用200 mg恩他卡朋（每日3次或4次）。我们在第1、2和8天上午（上午8点）给药前以及之后每隔1小时直至下午6点评估患者的功能障碍情况，采用改良的统一帕金森病评定量表运动部分。在上午服药前及服药后4小时内多次采集血样，用于恩他卡朋、左旋多巴及其代谢产物的药代动力学评估。与左旋多巴单药治疗相比，加用恩他卡朋后，从第1天到第8天临床功能障碍减轻了约16%（p<0.05）。单次服用恩他卡朋后，左旋多巴的曲线下面积（AUC）增加了38%（p<0.01），多次服用恩他卡朋7天后增加了40%（p<0.05）。恩他卡朋未改变左旋多巴的达峰时间（Tmax）和峰浓度（Cmax）值。与单用左旋多巴治疗相比，恩他卡朋治疗7天后，3-O-甲基多巴的AUC降低了44%（p<0.01），高香草酸的AUC降低了26%（p<0.05）。4例患者在恩他卡朋治疗期间比治疗前出现了稍多的运动障碍。根据血流动力学和安全性变量无显著变化判断，恩他卡朋与左旋多巴联合用药耐受性良好。（摘要截选至250字）
