Sustained release antiparkinson agents: controlled release levodopa.

The rationale for sustained release oral levodopa preparations is to deliver levodopa in the areas of maximal intestinal absorption in a slow and predictable way, leading to stable plasma levodopa levels and brain dopamine levels, therefore resulting in a lengthened duration of action. Sinemet CR is the prototype of such preparations, with demonstrated efficacy in decreasing periods of akinesia in parkinsonian patients with mild to moderate motor fluctuations. Total doses of levodopa are raised 10 to 30% because of the lowered bioavailability; diphasic dyskinesias may increase at the end of the day. Tolerance is good in de novo patients and studies are in progress to establish if early treatment with Sinemet CR delays the onset or attenuates the severity of motor fluctuations as compared to standard Sinemet.