Ghika J, Gachoud J P, Gasser U
Service de Neurologie, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Clin Neuropharmacol. 1997 Apr;20(2):130-9. doi: 10.1097/00002826-199704000-00004.
To improve the response of parkinsonian patients to L-Dopa treatment, a new preparation of L-Dopa/benserazide with dual-release properties was developed. The breakable three-layer tablets with biphasic dissolution kinetics combine the advantages of the standard and sustained-release formulations. The clinical efficacy of this new formulation was assessed in an open-label, pilot study for 14 weeks conducted by Swiss neurologists. Sixty-one parkinsonian patients were included: 5 (8%) patients were de novo, 39 (64%) had fluctuations, and 17 (28%) without fluctuations. The mean Hoehn and Yahr stage was 2.6 and the mean duration of disease was 7.4 years. The best prestudy treatment was kept stable for 2 weeks before entering the first 8-week period in which standard and/or sustained L-Dopa treatment could be either entirely or partially substituted by the dual-release formulation, which was as far as possible kept unchanged during the second 6-week period. During the substitution period, the overall dose of L-Dopa was significantly increased by 11.5%, probably reflecting some differences in the bioavailability of the various galenical formulations, and the mean daily drug intakes were reduced from 5.4 at baseline to 4.1 at week 8 (a 24% reduction, p < 0.001). Sixteen percent of the patients dropped out of the study because of unsatisfactory results, but none left for safety reasons. At the end of the study, complete substitution was attained in 71% of the patients. The remaining 27% combined the dual-release formulation with standard and/or sustained-release L-Dopa. The efficacy of treatment was assessed with the Webster Score and qualified with a mean decrease of 27% (p < 0.001) between baseline and week 14. A significant decrease of the reported adverse events such as dyskinesias and end-of-dose or wearing-off akinesias was also observed before (27 patients, 44%) and after (9 patients, 17%) the substitution (p < 0.02). These results infer that the dual-release formulation is as good as or superior to any other galenic form of L-Dopa. In conclusion, the dual-release formulation of L-Dopa either introduced or substituted for the best treatment available showed good clinical efficacy and tolerability in all stages of the evolution of idiopathic Parkinson's disease treatment in this 14-week open-label study.
为提高帕金森病患者对左旋多巴治疗的反应，研发了一种具有双相释放特性的左旋多巴/苄丝肼新制剂。具有双相溶解动力学的可破碎三层片剂结合了标准制剂和缓释制剂的优点。瑞士神经科医生进行了一项为期14周的开放标签试点研究，评估了这种新制剂的临床疗效。纳入了61例帕金森病患者：5例（8%）为初发患者，39例（64%）有症状波动，17例（28%）无波动。平均Hoehn和Yahr分期为2.6，平均病程为7.4年。在进入第一个8周疗程前，将最佳的研究前治疗方案维持稳定2周，在此期间，标准和/或缓释左旋多巴治疗可全部或部分被双相释放制剂替代，在第二个6周疗程中尽可能保持不变。在替代期，左旋多巴的总剂量显著增加了11.5%，这可能反映了各种剂型生物利用度的一些差异，平均每日药物摄入量从基线时的5.4降至第8周时的4.1（降低了24%，p<0.001）。16%的患者因效果不理想退出研究，但无人因安全原因退出。研究结束时，71%的患者实现了完全替代。其余27%的患者将双相释放制剂与标准和/或缓释左旋多巴联合使用。用韦伯斯特评分评估治疗效果，基线至第14周平均下降27%（p<0.001）。在替代前（27例患者，44%）和替代后（9例患者，17%）还观察到报告的不良事件如运动障碍和剂末或症状波动期运动不能显著减少（p<0.02）。这些结果表明双相释放制剂与左旋多巴的任何其他剂型一样好或更优。总之，在这项为期14周的开放标签研究中，引入或替代最佳可用治疗方案的左旋多巴双相释放制剂在特发性帕金森病治疗的所有阶段均显示出良好的临床疗效和耐受性。
