On‐off phenomenon: Relation to levodopa pharmacokinetics and pharmacodynamics

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Abstract
Motor function in the moderately to severely affected parkinsonian patient is critically dependent upon delivery of levodopa to the striatum. This, in turn, is influenced by the fluctuating plasma concentrations of levodopa produced by the drug's short half‐life and erratic absorption, and by modifiable transport at the blood‐brain barrier. Duration of response to a single dose of levodopa is proportional to peak plasma drug levels, and paradoxical responses may occur when plasma concentrations are in the vicinity of minimum effective concentrations. Thus the strategy of administering frequent, small doses of levodopa may contribute additional unpredictability to a fluctuating clinical response imposed by pharmacokinetic factors.