Continuous L-dopa infusion

Abstract

Continuous dopaminergic stimulation (CDS) is the predominant pharmacotherapeutic strategy in Parkinson's disease (PD). Levodopa is the most effective anti-PD drug but CDS is not achievable with oral formulations due to the short elimination half-life of levodopa. In advanced PD, motor performance is strongly correlated to plasma concentrations of levodopa, thus stable plasma levels are required for optimal effect. Intravenous infusion is the most reliable route of administration, but it is impractical for long-term therapy. Enteral (duodenal/jejunal) infusion of a gel formulation of levodopa/carbidopa has been studied since 1991. A pharmacokinetic trial showed that the enteral infusion provided significantly less fluctuations in plasma levodopa compared to oral sustained-release tablets. Motor performance was significantly more stable, because severe 'off' episodes could be avoided, in a trial comparing infusion as monotherapy with individualised combination therapies. Long-term follow-ups, in total more than 200 patient-years, have not shown any unexpected side-effects. Technical problems with the infusion system were rather common but may be overcome with new techniques for tubing. The infusion therapy is intended for daytime use but a few patients with severe nocturnal akinesia have successfully been treated with levodopa infusion 'around-the-clock' for up to 3 years. The 14-year-long experience suggests that enteral levodopa infusion is a safe and efficacious alternative to treat motor fluctuations and dyskinesias in advanced PD patients.