Pharmacokinetics and pharmacodynamics of levodopa

The pharmacokinetics and pharmacodynamics of levodopa are dominated by two features: the short plasma half-life of the drug and the portion of the antiparkinsonian response that parallels the plasma levodopa levels, the so-called short-duration response. These features are the basis of motor fluctuations that complicate long-term therapy with levodopa. Motor fluctuations will predictably improve with measures that prolong the elevations of plasma levodopa or prolong the efficacy of dopamine synthesized from exogenous levodopa. Because dyskinesia is closely linked to the short-duration response and conceivably part of the short-duration response, it is less clear that dyskinesia will be improved by therapeutic strategies that reduce motor fluctuations.