Soluble and controlled-release preparations of levodopa: do we really need them?

The controlled-release preparations of levodopa or newer soluble preparations of levodopa may improve levodopa bioavailability and tolerability and help managing (or even preventing) motor complications. Whether the controlled-release preparations or soluble preparations can really take the place of standard levodopa remains highly controversial, especially in patients receiving chronic levodopa therapy. Controlled-release formulations have a longer half-life and provide more stable plasma levels than standard levodopa. In de novo parkinsonian patients, controlled-release levodopa and standard levodopa are equally efficacious, and carry similar motor complication rates. In patients with advanced disease, whether motor fluctuations respond better to controlled release than to standard oral levodopa remains unclear. In selected parkinsonian patients, single bedtime doses of controlled-release levodopa may improve sleep and nocturnal disability. The poor solubility of levodopa may be overcome by soluble formulations that achieve maximal absorption. A levodopa formulation that guarantees faster and more reliable absorption would be especially useful in the clinical treatment of Parkinson's disease patients experiencing "no-on" or "delayed-on" phenomena. However, further studies with these new formulations are needed to understand if they offer better benefit to parkinsonian patients. New dual formulations incorporating both a faster absorption and an increased half-life than standard levodopa are currently under study.