Müller Thomas, Woitalla Dirk, Goetze Oliver, Erdmann Christoph
Department of Neurology, St. Joseph Hospital Berlin-Weissensee, Berlin, Germany.
Mov Disord. 2008 Jul 30;23(10):1458-61. doi: 10.1002/mds.22176.
Entacapone (EN) improves the efficacy of levodopa/dopadecarboxylase inhibitor (LD/DDI) formulations by inhibition of the enzyme catechol-O-methyltransferase (COMT). COMT inhibition also promotes the synthesis of basic LD metabolites, whereas DDI support the composition of acidic LD derivatives. LD metabolism correlates to the one of (13)C-sodium-octanoate, which is employed in breath tests to measure gastric emptying velocity. Objectives were to investigate the impact of COMT inhibition on the recovery rate of (13)C-sodium-octanoate in parkinsonian patients, who received first 100 mg LD/Carbidopa (CD) and the next day 100 mg LD/CD/EN combined with (13)C-sodium-octanoate in each case. The recovery rate of (13)C-sodium-octanoate was significant higher during the LD/CD/EN-compared with the LD/CD condition. COMT inhibition combined with LD/DDI improves absorption of a co-administered salt probably due to a COMT inhibition induced basic environment in gastrointestinal membranes. This improves dissolution and absorption of acids and salts. Thus it may enhance absorption of LD itself.
恩他卡朋(EN)通过抑制儿茶酚-O-甲基转移酶(COMT)来提高左旋多巴/多巴脱羧酶抑制剂(LD/DDI)制剂的疗效。COMT抑制还能促进LD碱性代谢物的合成,而DDI则有助于酸性LD衍生物的形成。LD代谢与用于呼吸试验以测量胃排空速度的(13)C-辛酸钠的代谢相关。目的是研究COMT抑制对帕金森病患者(13)C-辛酸钠回收率的影响,这些患者先接受100mg LD/卡比多巴(CD),次日在每种情况下接受100mg LD/CD/EN并联合(13)C-辛酸钠。与LD/CD情况相比,在LD/CD/EN期间,(13)C-辛酸钠的回收率显著更高。COMT抑制与LD/DDI联合使用可能由于COMT抑制在胃肠膜中诱导的碱性环境而改善了共同给药盐的吸收。这改善了酸和盐的溶解与吸收。因此,它可能增强LD自身的吸收。