Optimization of use of levodopa in Parkinson's disease: role of levodopa-carbidopa-entacapone combination
Castro A., Valldeoriola F., Linazasoro G., Rodríguez-Oroz M.C. (1), Stochi F., Marín C., Rodríguez M., Vaamonde J., Jenner P., Álvarez L., Pavón N., Macías R., Luquin M.R. (1), Hernández B., Grandas F., Giménez-Roldán S., Tolosa E., Obeso J.A. (1)
Levodopa remains the mainstay treatment for Parkinson's disease (PD).
Chronic treatment is associated with motor complications (MC) that marred the clinical benefit of levodopa. These problems and experimental data in cell cultures indicating a neurotoxic effect of levodopa have led to the idea of delaying the introduction of levodopa treatment for as long as possible. We here review recent data regarding the mechanism of action of levodopa and its application in clinical practice on the light of the marketing of the combination levodopa-carbidopa- entacapone.
Accumulated evidence indicates that MC are mainly the consequence of disease severity governing the degree of dopaminergic depletion and the pulsatile dopaminergic stimulation provided by levodopa short plasma half-life. There is no in vivo or clinical evidence of a relevant neurotoxic effect of levodopa. In fact, the recent ELLDOPA study may suggest a neuroprotective effect. Entacapone reduces homocysteine plasma levels which could provide a mechanism to reduce cell death in PD. Currently, the combination levodopa-carbidopa-entacapone is particularly indicated for the treatment of wearing off fluctuations. Experimental evidence suggests that early treatment with levodopa-carbidopa-entacapone may substantially ameliorate the incidence of MC.
Such a clinical study in de novo patients is underway. At present, the combination levodopa-carbidopa-entacapone is indicated when levodopa is judged necessary.
CITATION Neurologia. 2005 May;20(4):180-8