LEVODOPA ETHYLESTER - A NOVEL RESCUE THERAPY FOR RESPONSE FLUCTUATIONS IN PARKINSONS-DISEASE

In Parkinson's disease (PD), response fluctuations may be due, in part , to pharmacokinetic problems including poor solubility of levodopa an d difficulties in its absorption. We administered levodopa ethylester (LDEE), a new highly soluble prodrug of levodopa, by subcutaneous and intramuscular injections to PD patients with response fluctuations, in an open trial to examine its safety and efficacy. Various doses of LD EE (150-400 mg) turned patients ''on'' with a high success rate (43 of 45 injections). Latencies to ''turning on'' decreased and duration of on responses increased in a dose-dependent manner. LDEE, given either subcutaneously or intramuscularly, produced similar beneficial effect s and induced rapid and sustained elevations in plasma levodopa levels . The drug was well tolerated with only minor and negligible side effe cts. Study suggests that subcutaneous and intramuscular administration of LDEE may be advantageous as a novel therapeutic strategy for respo nse fluctuations. It may be particularly useful to rapidly and predict ably rescue patients from a variety of disabling ''off'' situations.