Continuous versus intermittent oral administration of levodopa in Parkinson's disease patients with motor fluctuations: A pharmacokinetics, safety, and efficacy study

Background: Laboratory and clinical evidence indicate that continous delivery of levodopa is associated with reduced motor complications compared to standard intermittent levodopa.Objective: To assess the pharmacokinetics and efficacy of continuous oral delivery of L-dopa/carbidopa in PD patients with motor fluctuations.Methods: Eighteen PD patients with motor fluctuations were enrolled in an open-label study comparing pharmacokinetics and efficacy measures between standard intermittent oral L-dopa/carbidopa and "continuous" oral L-dopa/carbidopa. Continuous treatmentwas operationally defined as sips of an L-dopa dispersion at 5-to 10-minute intervals. On day 1, patients received their usual oral L-dopa/carbidopa doses. On day 2, patients received L-dopa/carbidopa dose by "continuous" oral administration. On day 3, patients received a single dose of oral L-dopa/carbidopa followed by continuous administration of L-dopa/carbidopa. Each study period was 8 hours, and the total L-dopa/carbidopa dose administered was the same on each day. Analyses of variability were primarily-based samples drawn between 4 and 8 hours when subjects were in a relative steady state.Results: There was less variability in plasma L-dopa concentration with continuous versus intermittent oral L-dopa/carbidopa treatment (fluctuation index was 0.99 +/- 0.09 vs. 1.38 +/- 0.12 [P < 0.001] and coefficient of variation was 0.35 +/- 0.03 vs. 0.49 +/- 0.04 [P < 0.001]). Mean OFF time was decreased by 43% (P < 0.001) with continuous oral L-dopa therapy. No safety or tolerability issues were observed.Conclusions: Continuous oral delivery of L-dopa/carbidopa was associated with less plasma variability and reduced off time in comparison to standard intermittent oral L-dopa/carbidopa therapy. (c) 2019 International Parkinson and Movement Disorder Society