PHARMACOKINETIC MODEL OF ORAL LEVODOPA AND ROLE OF CARBIDOPA IN PARKINSONIAN-PATIENTS

A pharmacokinetic model of oral levodopa is proposed to elucidate the effects of carbidopa on the pharmacokinetics of levodopa, The propriet y of the model was evaluated by simultaneous computer Multi-Line fitti ng for the plasma concentration-time data of levodopa and dopamine-3-O -sulfate (DA-S), a major metabolite of levodopa, after oral administra tion of three different levodopa doses to parkinsonian patients, Plasm a profiles of levodopa acid DA-S were also determined in 12 parkinsoni an patients during daily oral administration of Neodopaston(R), a levo dopa preparation containing carbidopa in tablet form, We investigated the role of carbidopa by comparing the populational mean parameters ca lculated in the levodopa alone model with those obtained in patients c oadministered levodopa and carbidopa, The results indicated that the p harmacokinetics of levodopa coadministered with carbidopa were dose-in dependent and that carbidopa reduces the first-pass metabolism of levo dopa in the gut wall to less than 10% of the dose absorbed, and decrea ses the systemic clearance of levodopa by 35-39%. The proposed pharmac okinetic model and the evaluation of carbidopa in this study will prov ide useful information for the development of drug delivery systems fo r levodopa or catechol-O-methyltransferase inhibitors, for further sta bilization of plasma concentrations of levodopa in parkinsonian patien ts.