Disease progression and pharmacodynamics in Parkinson disease - evidence for functional protection with levodopa and other treatments.
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.
Holford
Nicholas H G
NH
Department of Pharmacology & Clinical Pharmacology, University of Auckland, Auckland, New Zealand. n.holford@auckland.ac.nz
Chan
Phylinda L S
PL
Nutt
John G
JG
Kieburtz
Karl
K
Shoulson
Ira
I
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
D000978:Antiparkinson Agents; D018491:Dopamine Agonists; D010479:Pergolide; D012642:Selegiline; D001971:Bromocriptine; D007980:Levodopa