Mizuno Yoshikuni, Yamamoto Mitsutoshi, Kuno Sadako, Hasegawa Kazuko, Hattori Nobutaka, Kagimura Tatsuro, Sarashina Akiko, Rascol Olivier, Schapira Anthony H V, Barone Paolo, Hauser Robert A, Poewe Werner
Department of Neuroregenerative Medicine, Kitasato University School of Medicine, Kanagawa, Japan.
Clin Neuropharmacol. 2012 Jul-Aug;35(4):174-81. doi: 10.1097/WNF.0b013e31825f77b9.
To compare the efficacy, safety, tolerability, and trough plasma levels of pramipexole extended-release (ER) and pramipexole immediate-release (IR), and to assess the effects of overnight switching from an IR to an ER formulation, in L-dopa-treated patients with Parkinson disease (PD).
After a 1- to 4-week screening/enrollment, 112 patients who had exhibited L-dopa-related problems or were receiving suboptimal L-dopa dosage were randomized in double-blind, double-dummy, 1:1 fashion to pramipexole ER once daily or pramipexole IR 2 to 3 times daily for 12 weeks, both titrated to a maximum daily dose of 4.5 mg. Successful completers of double-blind treatment were switched to open-label pramipexole ER, beginning with a 4-week dose-adjustment phase.
Among the double-blind treatment patients (n = 56 in each group), Unified Parkinson's Disease Rating Scale Parts II+III total scores decreased significantly from baseline and to a similar degree with pramipexole ER and IR formulations. In each group, 47 double-blind patients (83.9%) reported adverse events (AEs), requiring withdrawal of 3 ER patients (5.4%) and 2 IR patients (3.6%). Trough plasma levels at steady state (at the same doses and dose-normalized concentrations) were also similar with both formulations. Among open-label treatment patients (n = 53 from IR to ER), 83% were successfully switched (no worsening of PD symptoms) to pramipexole ER.
In L-dopa-treated patients, pramipexole ER and pramipexole IR demonstrated similar efficacy, safety, tolerability, and trough plasma levels. Patients can be safely switched overnight from pramipexole IR to pramipexole ER with no impact on efficacy.
比较普拉克索缓释剂（ER）和普拉克索速释剂（IR）的疗效、安全性、耐受性及谷血浆浓度，并评估左旋多巴治疗的帕金森病（PD）患者从IR制剂夜间转换为ER制剂的效果。
经过1至4周的筛查/入组后，112例出现左旋多巴相关问题或接受次优左旋多巴剂量的患者，以双盲、双模拟、1:1的方式随机分为每日一次普拉克索ER组或每日2至3次普拉克索IR组，治疗12周，两者均滴定至最大日剂量4.5mg。双盲治疗的成功完成者转换为开放标签的普拉克索ER，从4周的剂量调整期开始。
在双盲治疗患者中（每组n = 56），统一帕金森病评定量表II+III部分的总分较基线显著下降，普拉克索ER和IR制剂下降程度相似。每组中，47例双盲患者（83.9%）报告了不良事件（AE），3例ER患者（5.4%）和2例IR患者（3.6%）因不良事件退出。两种制剂在稳态时的谷血浆浓度（在相同剂量和剂量标准化浓度下）也相似。在开放标签治疗患者中（53例从IR转换为ER），83%成功转换为普拉克索ER（帕金森病症状无恶化）。
在左旋多巴治疗的患者中，普拉克索ER和普拉克索IR在疗效、安全性、耐受性和谷血浆浓度方面表现相似。患者可从普拉克索IR夜间安全转换为普拉克索ER，且对疗效无影响。
