"Wearing-off" effect, the most common form of levodopa-induced fluctuations, 
seems to be related to the short plasma half-life of the drug. More sustained 
plasma levodopa levels may be achieved with a new controlled-release formulation 
of carbidopa/levodopa, Sinemet CR4. We studied 20 patients, 12 men and 8 women, 
with Parkinson's disease complicated by "wearing-off" phenomenon. Mean age was 
61.1 +/- 8.1 years, duration of symptoms 8.3 +/- 2.4 years, and the Hoehn-Yahr 
stage 3.0 +/- 0.9. In a 12-week double-blind study, the average number of 
tablets administered per day decreased from 5.7 +/- 1.2 to 3.8 +/- 0.7 when 
Sinemet CR4 (50/200) was substituted for the standard Sinemet (25/100) (p less 
than 0.001). However, this was at the expense of reducing the "on" time (without 
dyskinesia) from 9.3 +/- 4.6 to 7.5 +/- 4.3 (p less than 0.05), although the 
total "on" time did not significantly change. In a long-term follow-up of 18 
patients, the "on" time with dyskinesia and morning dystonia significantly 
increased (p less than 0.05). There was no significant change in the total daily 
dosage of levodopa, but the daily number of doses and tablets significantly 
decreased (p less than 0.001). Despite increased dyskinesia, most patients 
preferred taking fewer tablets and have elected to continue taking Sinemet CR4 
instead of standard Sinemet. Sinemet CR4 seems to offer a new and effective 
strategy for the management of levodopa-related fluctuations.