Steady plasma levodopa concentrations required for good clinical response to CR-4 in patients with 'on-off'.

Ten patients with Parkinson's disease and severe motor fluctuations were given Sinemet (25/100) for 4 weeks followed by 4 weeks of Sinemet (CR-4). After each drug preparation was optimized, patients were rated by neurological examination and plasma levodopa (LD) measured at hourly intervals (9 a.m.-4 p.m.). For the group as a whole, variations throughout the day of plasma LD and clinical state were no different on the 2 formulations. Three patients whose fluctuations responded well to CR-4 had either much less variable plasma LD levels on CR-4 or were able to maintain plasma LD above a minimum threshold. In severe fluctuators, a major benefit from CR-4 can be expected only in those patients who can maintain steady plasma LD levels above the threshold for achieving the 'on' state.