Prolonged serum levodopa levels with controlled-release carbidopa-levodopa in the treatment of Parkinson's disease.

Twenty parkinsonian patients (Hoehn and Yahr scale, I through III) were treated with controlled-release carbidopa-levodopa (CR-2 or CR-3) and standard carbidopa-levodopa (Sinemet, 25 mg/100 mg) in a double-blind, crossover pharmacokinetic and clinical efficacy study. The controlled-release agents had a slower rise to peak plasma values and flatter pharmacokinetic curves than did the standard. The area under the curve for CR-3 was significantly increased by 55.5% as compared with standard agent and by 84.2% as compared with CR-2. No differences in clinical efficacy were found between controlled-release agents and the standard agent for this group of parkinsonian patients with mild to moderate severity. The dissociation between the prolonged serum levodopa levels and unimproved clinical efficacy may have resulted from the absence of patients with prominent motor fluctuations and/or substantial serum levodopa variability that was especially prominent with CR-3.