Relationship between levodopa concentration, dyskinesias, and motor effect in parkinsonian patients: a 3-year follow-up study.

We conducted a 3-year prospective assessment of the relationship between levodopa (L-DOPA) plasma concentration and both dyskinesias and tapping motor response after a standard oral L-DOPA dose in 11 parkinsonian patients, Hoehn & Yahr (H & Y) stages 2-3, with L-DOPA therapeutic response complicated by involuntary movements. Over the 3-year period, duration of the tapping effect significantly decreased, while that of dyskinesias showed minor changes. Initially, the L-DOPA therapeutic response significantly outlasted the dyskinesia effect and progressively shortened to parallel the dyskinesia profile at the more advanced clinical stage. According to kinetic-dynamic modeling, L-DOPA concentrations producing 50% of maximum therapeutic and toxic effects (EC50) also changed independently. EC50 for dyskinesias did not vary over time. EC50 for the tapping effect was, at the first observation, significantly lower than that of the matched value for dyskinesias and progressively rose to values similar to the EC50 for dyskinesias by the third year of follow-up. These data suggest a dissociation of the kinetic-dynamic relationship of L-DOPA motor and dyskinesia effects, possibly reflecting different cerebral handling of exogenous levodopa-derived dopamine with disease progression.