Holford Nicholas H G, Chan Phylinda L S, Nutt John G, Kieburtz Karl, Shoulson Ira
Department of Pharmacology & Clinical Pharmacology, University of Auckland, Auckland, New Zealand.
J Pharmacokinet Pharmacodyn. 2006 Jun;33(3):281-311. doi: 10.1007/s10928-006-9012-6. Epub 2006 Apr 20.
We have modelled the Unified Parkinson's Disease Rating Scale (UPDRS) scores collected in 800 subjects followed for 8 years. Newly diagnosed and previously untreated subjects were initially randomized to treatment with placebo, deprenyl, tocopherol or both and, when clinical disability required, received one or more dopaminergic agents (levodopa (carbidopa/levodopa), bromocriptine, or pergolide). Using models for disease progression and pharmacodynamic models for drug effects we have characterized the changes in UPDRS over time to determine the influence of the various drug treatments. We have confirmed and quantitated the relative symptomatic benefits of the dopaminergic agents and provide model-based evidence for slowing of disease progression.
我们对800名随访8年的受试者所收集的统一帕金森病评定量表（UPDRS）评分进行了建模。新诊断且先前未接受治疗的受试者最初被随机分配接受安慰剂、司来吉兰、维生素E或两者联合治疗，当临床残疾需要时，接受一种或多种多巴胺能药物（左旋多巴（卡比多巴/左旋多巴）、溴隐亭或培高利特）治疗。利用疾病进展模型和药物效应的药效学模型，我们已描绘出UPDRS随时间的变化情况，以确定各种药物治疗的影响。我们已证实并量化了多巴胺能药物的相对症状改善效果，并为疾病进展的减缓提供了基于模型的证据。
