Controlled Release Levodopa-Carbidopa (CR-5) in the Management of Parkinsonian Motor Fluctuations

Parkinsonian patients receiving long-term levodopa-carbidopa (Sinemet) therapy often develop fluctuations in motor performance. Although maintenance of stable levels of plasma levodopa by means of its continuous intravenous infusion diminishes these fluctuations, practical limitations attending this therapeutic approach have prompted continuing attempts to develop oral controlled release levodopa-carbidopa formulations. In a double-blind, crossover clinical trial, one such preparation, CR-5 (Merck, Sharp & Dohme), produced significantly less plasma levodopa variations and substantially improved motor performance over Sinemet in 15 patients with mild to moderate fluctuations, all but one of whom chose to continue on CR-5 therapy after the study. Eight patients with severe motor fluctuations could not adjust to this preparation during the open phase and consequently withdrew from the study. Subjectively, most patients noted the convenience of less frequent dosing, improved sleep, and the amelioration of early morning akinesia and dystonia.