Clin Neuropharmacol. 1999 Jul-Aug;22(4):220-5.
This study was designed to determine whether remacemide hydrochloride, a noncompetitive N-methyl-D-aspartate-type glutamate receptor channel blocker, has a significant impact on serum levodopa concentrations that could complicate the interpretation of future clinical trial results. We performed a multicenter, open-label study of remacemide in 18 patients with mild to moderate Parkinson's disease (PD) who were taking stable dosages of levodopa. Levodopa pharmacokinetics were determined after administration of the patients' usual morning levodopa dose. Patients then took remacemide 300 mg twice a day for 2 weeks, with levodopa pharmacokinetics determined again at an identical testing session, except that remacemide 300 mg was administered one hour before levodopa. Clinical responses were also measured using the Unified Parkinson's Disease Rating Scale (UPDRS). With remacemide treatment, the area-under-the-curve for levodopa did not change. The mean peak plasma levodopa concentration (Cmax) was reduced by 16% compared to baseline, and the mean time to achieve peak plasma levodopa concentration (Tmax) was delayed by 20%. Although remacemide delayed levodopa absorption, the magnitude of the interaction suggests that is unlikely to be an important factor in planning and interpreting future trials of remacemide in levodopa-treated patients with PD.
本研究旨在确定盐酸瑞马西胺(一种非竞争性N-甲基-D-天冬氨酸型谷氨酸受体通道阻滞剂)是否会对血清左旋多巴浓度产生显著影响,而这可能会使未来临床试验结果的解读变得复杂。我们对18例正在服用稳定剂量左旋多巴的轻度至中度帕金森病(PD)患者进行了一项多中心、开放标签的瑞马西胺研究。在给予患者常规早晨左旋多巴剂量后,测定左旋多巴的药代动力学。然后患者每天两次服用300毫克瑞马西胺,持续2周,在相同的测试环节再次测定左旋多巴药代动力学,但瑞马西胺300毫克在左旋多巴前1小时给药。还使用统一帕金森病评定量表(UPDRS)测量临床反应。接受瑞马西胺治疗后,左旋多巴的曲线下面积没有变化。与基线相比,血浆左旋多巴平均峰值浓度(Cmax)降低了16%,达到血浆左旋多巴峰值浓度的平均时间(Tmax)延迟了20%。虽然瑞马西胺延迟了左旋多巴的吸收,但这种相互作用的程度表明,在计划和解读未来对接受左旋多巴治疗的PD患者进行的瑞马西胺试验时,这不太可能是一个重要因素。