title: Disease progression and pharmacodynamics in Parkinson disease - evidence for functional protection with levodopa and other treatments.
abstract: 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.
authors.affiliation: Department of Pharmacology & Clinical Pharmacology, University of Auckland, Auckland, New Zealand. n.holford@auckland.ac.nz
authors.forename: Nicholas H G
authors.initials: NH
authors.lastname: Holford
authors.forename: Phylinda L S
authors.initials: PL
authors.lastname: Chan
authors.forename: John G
authors.initials: JG
authors.lastname: Nutt
authors.forename: Karl
authors.initials: K
authors.lastname: Kieburtz
authors.forename: Ira
authors.initials: I
authors.lastname: Shoulson
mesh_terms: D000465:Algorithms; D000978:Antiparkinson Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D001499:Bayes Theorem; D001971:Bromocriptine / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D018450:Disease Progression; D018491:Dopamine Agonists / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D006801:Humans; D007980:Levodopa / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D008954:Models, Biological; D010300:Parkinson Disease / Q000188:drug therapy* / Q000473:pathology; D010479:Pergolide / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D012642:Selegiline / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000978:Antiparkinson Agents; D018491:Dopamine Agonists; D010479:Pergolide; D012642:Selegiline; D001971:Bromocriptine; D007980:Levodopa