行政院國家科學委員會專題研究計畫成果報告:COMT抑制劑entacapone對於巴金森氏病患者的血清catecholamine濃度及心臟血管系統的影響

Abstract

COMT 抑制劑代表一種新的抗巴病藥物種類。Entacapone 是一個有效的、選擇 性的、可逆性的、口服的及作用在週邊系統的新一代COMT 抑制劑。此藥已經在臨 床上被證明能夠改善巴病患者藥效減弱的現象，增加血中左多巴的有效濃度面積及下 降3-OMD 的含量。由於體內的catecholamines ， 如norepinephrine(NE) 及 epinephrine(EP)也是經由COMT 來代謝，理論上服用COMT 抑制劑後也可能增加血 中NE 及EP 的濃度進而影響心跳、血壓及其他相關的心臟血管系統的反應，尤其是 在巴病患者原本就經常合併交感神經系統異常的情況下，更需留意服用entacapone 後這一方面的副作用。除此之外，我們先前的研究發現COMT 酵素的基因多形性會 影響巴病患者對另一類COMT 抑制劑tolcapone 的藥效反應，具有野生形高活性 (COMT H/H)的基因形態的病人服用tolcapone 6 週後停電期(off time)較COMT H/L 或 COMT L/L 基因形減少許多。因此在本研究，我們探討COMT 基因多形性是否會影響 巴病患者服用entacapone 後血中catecholamine 之變化及臨床上心臟血管功能的改 變。我們的研究結果發現，COMT 抑制劑的服用對受試者之心跳、血壓及血中 catecholamine 的濃度變化，並無顯著的影響。

This study is an open label, and single-arm study that will evaluate the changes in the plasma concentrations of norepinephrine and epinephrine after the co-administration of single dose of entacapone and L-dopa/AADC inhibitor in PD patients. On the first day of pharmacokinetic evaluation, patients took only their individual, standard dose of levodopa（Sinemetâ or Madoparâ）; On the second day, a single dose of entacapone 200 mg was coadministered with levodopa. Venous blood samples were taken immediately before test dose and at different time points thereafter within two days. Plasma concentration of plasma concentration of catecholamine were measured by reverse-phase high-performance liquid chromatography with electrochemical detector. Moreover, blood pressure and heart rate were measured to evaluate the safety of entacapone. In the present study, we did not see a significant change in the heart rate, blood pressure and plasma concentration of catecolamine after the administration of entacapne, suggesting a well toleration in the hemodynamic system.