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A pharmacokinetic model of oral levodopa is proposed to elucidate the effects of carbidopa on the pharmacokinetics of levodopa. The propriety of the model was evaluated by simultaneous computer Multi-Line fitting for the plasma concentration-time data of levodopa and dopamine-3-O-sulfate (DA-S), a major metabolite of levodopa, after oral administration of three different levodopa doses to parkinsonian patients. Plasma profiles of levodopa and DA-S were also determined in 12 parkinsonian patients during daily oral administration of Neodopaston, a levodopa preparation containing carbidopa in tablet form. We investigated the role of carbidopa by comparing the populational mean parameters calculated in the levodopa alone model with those obtained in patients coadministered levodopa and carbidopa. The results indicated that the pharmacokinetics of levodopa coadministered with carbidopa were dose-independent and that carbidopa reduces the first-pass metabolism of levodopa in the gut wall to less than 10% of the dose absorbed, and decreases the systemic clearance of levodopa by 35-39%. The proposed pharmacokinetic model and the evaluation of carbidopa in this study will provide useful information for the development of drug delivery systems for levodopa or catechol-O-methyltransferase inhibitors, for further stabilization of plasma concentrations of levodopa in parkinsonian patients.

Pharmacokinetic Model of Oral Levodopa and Role of Carbidopa in Parkinsonian Patients.