The levodopa wearing-off phenomenon in Parkinson's disease: pharmacokinetic considerations

Levodopa is the most efficacious treatment in the management of Parkinson's disease. Unfortunately, chronic use of traditional levodopa/dopa decarboxylase inhibitor formulations is associated with the development of complications, such as wearing-off and dyskinesia. In an attempt to avoid these complications, some physicians delay the introduction of levodopa or employ levodopa-sparing strategies; however, these strategies are frequently suboptimal for patients. As most patients require the superior efficacy of levodopa during the course of their disease, an appreciation of the changing response to levodopa over time and an understanding of the pharmacokinetic principles underlying the development of complications such as wearing-off is essential in the long-term management of the patient.