SUSTAINED-RELEASE OF LEVODOPA - SINGLE-DOSE STUDY OF A NEW FORMULATION

Motor fluctuations and dyskinesias in Parkinsonian patients may be at least partially due to fluctuations of levodopa plasma concentrations. Sustained-release (SR) formulations of levodopa may present a promisi ng, effective solution of this problem. Therefore we performed a 4-fol d, crossover double-blind trial with a new SR preparation, tested in h ealthy volunteers (Gerlach et al., 1988) before, in 12 Parkinsonian su bjects. Two different dosages of the pure new levodopa SR-preparation, a composition of 70% SR and 30% levodopa immediate release (IR) and a conventional IR levodopa preparation were compared by their pharmacok inetic behaviour and their clinical effects. The relative bioavailabil ity of levodopa in plasma was 69% for the combination of SR and IR lev odopa release, for the pure SR formulations (100 mg levodopa) 54% and (200 mg levodopa) 55%, compared to the 100% of the standard form of IR release of 100 mg levodopa. In contrast to the conventional IR formul ation the pharmacokinetic behaviour of the SR preparations showed no i nitial sharp peak, but more continuous and longer maintaining plasma c oncentrations of levodopa. Due to the small numbers of cases and the m issing homogenity of the selected patients no statistical significant differences between the four preparations regarding the clinical respo nse were observed. But the described pharmacokinetic behaviour gives h ope, that these newly developed SR-preparations may lead to progress i n the treatment of Parkinson's disease (prolongation of dosage interva ls, reduction of motor fluctuations).