Levodopa pharmacokinetics and pharmacodynamics in fluctuating parkinsonian patients

We investigated levodopa intravenous infusion rates, plasma concentrations, and clinical responses in 23 parkinsonian patients with a fluctuating response to the drug. There was a linear relationship between rate of levodopa infusion and plasma concentration when carbidopa was coadministered. Minimum-therapeutically effective plasma concentrations of levodopa ranged from 3 to 12 nmol/ml. The duration, but not the magnitude, of clinical response was linearly related to plasma concentrations. The clinical response lagged behind the rise and fall of plasma levodopa. There was no evidence of idiosyncratic pharmacokinetic or pharmacodynamic responses to levodopa to explain the fluctuating response.