Samanta Johan, Hauser Robert A
University of Arizona, Banner Good Samaritan Medical Center, Department of Neurology, College of Medicine, Phoenix, AZ 85258 USA.
Expert Opin Pharmacother. 2007 Apr;8(5):657-64. doi: 10.1517/14656566.8.5.657.
Motor fluctuations are a common problem in the long-term management of Parkinson's disease (PD), resulting in disability and impaired quality of life. The relatively short serum half-life (approximately 90 min) of oral levodopa/carbidopa and its erratic absorption due to delayed and inconsistent gastric emptying (a non-motor feature of PD) are thought to be important factors in the development of motor fluctuations. Continuous infusion of levodopa/carbidopa directly into the small intestine of PD patients results in marked reduction of motor fluctuations by reducing plasma levodopa variability by an order of magnitude over oral therapy. Previously, the use of long-term intraduodenal infusion of levodopa/carbidopa was limited by the relatively large volumes of infusate necessitated by the low solvency of levodopa. The development of a micronized levodopa (20 mg/ml) and carbidopa (5 mg/ml) suspension utilizing a methylcellulose gel provides the high levodopa concentration and physical and chemical stability necessary for long-term enteral therapy. Clinical evidence indicates that a marked reduction of motor fluctuations and dyskinesias can be achieved and maintained by intraduodenal administration of this suspension. This article reviews the published data describing the efficacy and safety of duodenal levodopa, and discusses its current and potential role in meeting the needs of PD patients.
运动波动是帕金森病(PD)长期管理中的常见问题,会导致残疾和生活质量受损。口服左旋多巴/卡比多巴的血清半衰期相对较短(约90分钟),且由于胃排空延迟和不一致(PD的一种非运动特征)导致其吸收不稳定,这些被认为是运动波动发生的重要因素。将左旋多巴/卡比多巴持续直接输注到PD患者的小肠中,通过使血浆左旋多巴变异性比口服治疗降低一个数量级,从而显著减少运动波动。以前,由于左旋多巴的低溶解性需要相对大量的输注液,长期十二指肠内输注左旋多巴/卡比多巴受到限制。利用甲基纤维素凝胶开发的微粉化左旋多巴(20毫克/毫升)和卡比多巴(5毫克/毫升)混悬液,为长期肠内治疗提供了所需的高左旋多巴浓度以及物理和化学稳定性。临床证据表明,通过十二指肠内给予这种混悬液可实现并维持运动波动和异动症的显著减少。本文综述了描述十二指肠左旋多巴疗效和安全性的已发表数据,并讨论了其在满足PD患者需求方面的当前和潜在作用。