儿茶酚—氧位-甲基转移酶(COMT)可代谢带有儿茶酚基团的化合物(如左旋多巴)。抑制COMT可阻止左旋多巴甲基化,减少3-氧-甲基多巴(3-OMD)的形成,因而可改善左旋多巴的药代动力学。通过稳定血浆左旋多巴浓度,COMT抑制剂可改善帕金森症病人对左旋多巴的疗效。两种有效的选择性、可逆性,可口服给药的COMT抑制剂,tolcapone(托卡朋)和entacapone(安托卡朋)正在临床试验中,在此对来自几项临床药理研究的数据作一总结和比较。tolcapone和entacapone对红细胞COMT活性的抑制作用均呈剂量依赖性。口服单剂200mg后,tolcapone和entacapone的最大抑制效应分别为90％和70％。与entacapone相比,tolcapone抑制作用的持续时间明显长一些。两种化合物均可增加左旋多巴的生物利用度,亦即血浆农度-时间曲线下面积(AUC)。对于tolcapone,最大作用(AUC增加94％)的剂量为200mg,而对于entacapone,其剂量为200mg和400mg时,AUC分别增加42％和65％。使用200mg tolcapone和entacapone后,血浆3-OMD浓度分别下降59％和45％。两种药物均可迅速吸收,在200mg时仍表现出线性药代动力学特性。entacapone的分布容积要大于tolcapone,从体内清除的速度更为迅速;因此,相似剂量的entacapone所产生血浆浓度要明显低于tolcapone,这有助于说明这两种COM Catechol-O-methyltransferase (COMT) can metabolize compounds with catechol groups (such as levodopa). Inhibition of COMT prevents levodopa methylation and reduces the formation of 3-O-methyl-D-dopa (3-OMD), thus improving the pharmacokinetics of levodopa. By stabilizing plasma levodopa concentration, COMT inhibitors can improve the efficacy of levodopa in patients with Parkinson’s disease. Two potent, selective, reversible, orally administrable COMT inhibitors, tolcapone and entacapone, are in clinical trials, where data from several clinical pharmacological studies are available A summary and comparison. The inhibitory effect of tolcapone and entacapone on COMT activity of erythrocytes were dose-dependent. The maximum inhibitory effects of tolcapone and entacapone were 90% and 70%, respectively, after a single oral dose of 200 mg. Compared with entacapone, tolcapone inhibitory effect was significantly longer duration. Both compounds increased the bioavailability of levodopa, that is, the area under the plasma-to-time curve (AUC). For tolcapone, the maximum effect (94% increase in AUC) was 200 mg, while for entacapone, the AUC increased by 42% and 65%, respectively, at doses of 200 mg and 400 mg. Plasma plasma 3-OMD decreased by 59% and 45%, respectively, after 200 mg of tolcapone and entacapone. Both drugs are rapidly absorbed and still exhibit linear pharmacokinetic properties at 200 mg. entacapone has a greater volume of distribution than tolcapone and clears more rapidly from the body; therefore, a similar dose of entacapone produces significantly lower plasma concentrations than tolcapone, which helps illustrate both COM