Clinical studies with and pharmacokinetic considerations of sustained-release levodopa.

Although levodopa is the most effective antiparkinson agent yet available, strategies for improving the constancy of levodopa delivery to the brain are sometimes needed to optimize its actions. Its most common formulation is Sinemet, a combination of levodopa and carbidopa. Conventional Sinemet is absorbed and metabolized over 3 to 4 hours; however, Sinemet CR, a sustained-release preparation of 200 mg of levodopa and 50 mg of carbidopa, offers a duration of effect almost double that of Sinemet 25/100. In an 8-week trial with 25 parkinsonian patients, those treated with Sinemet CR required fewer daily doses than with the conventional Sinemet formulation and experienced improved "on" times (although improvements were not evident in all motor-fluctuation situations). The best therapeutic strategy may be a combination of the two Sinemet preparations, conventional Sinemet 25/100 as a booster dose and Sinemet CR for more sustained effect.