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

摘要

ABSTRACT 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 treatment was 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. ? 2019 International Parkinson and Movement Disorder Society