Search

The pharmacokinetic advantage of controlled-release carbidopa-levodopa (Sinemet CR) is its slow dissolution and gradual absorption, resulting in more sustained plasma levodopa levels and higher plasma troughs. In patients with moderately severe disease, the benefits include less severe "wearing-off," a modest increase in daily "on" time, and fewer daily doses. Bioavailability of Sinemet CR levodopa is less than that of standard Sinemet, so a slightly higher total daily levodopa dose is required to achieve a comparable effect; but because Sinemet CR is absorbed much more slowly than is the standard preparation, dosing frequency can be reduced by up to half. For most patients, titration will be required after the transition has been made from standard to controlled-release Sinemet. The effect of Sinemet CR on dyskinesias is often difficult to predict and, in individual patients, may depend on the temporal pattern of dyskinesias being experienced. Success in using this new preparation depends on understanding its pharmacokinetic properties, judicious patient selection, and an effective program of patient education.

Sinemet CR, a controlled-release form of carbidopa/levodopa, was administered for 36 or 39 months to 8 patients with Parkinson's disease in an open-label study. On standard Sinemet each patient had experienced "wearing off" phenomena, and 5 had also experienced random "off" episodes. Daily "on" time, dyskinesia time, disability score, levodopa dosage requirement, and dosing frequency on Sinemet CR were compared with baseline values on standard Sinemet therapy. After both 3 and 36 or 39 months of Sinemet CR therapy, 5 patients showed increased daily "on" time compared with baseline. All 8 required fewer daily doses after 3 months on Sinemet CR, but only 3 were still taking fewer doses after 36 or 39 months. Disability scores remained essentially unchanged. Patients continued to elect to remain on Sinemet CR over the 3-year period, citing improved predictability of response and less severe and precipitous "off" episodes as the main reasons. This experience suggests that patient acceptance of Sinemet CR remains high. A modest improvement in "on" time can be achieved and maintained in some patients for as long as 3 years. However, as with standard Sinemet, dosing frequency for Sinemet CR may need to be gradually increased with time in order to maintain benefits achieved.