Continuous versus intermittent oral administration of levodopa in Parkinson's disease patients with motor fluctuations: A pharmacokinetics, safety, and efficacy study.
Pharmacokinetics
continous levodopa
motor complications
Journal
Movement disorders : official journal of the Movement Disorder Society
ISSN: 1531-8257
Titre abrégé: Mov Disord
Pays: United States
ID NLM: 8610688
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
12
07
2018
revised:
07
11
2018
accepted:
08
11
2018
pubmed:
18
1
2019
medline:
21
12
2019
entrez:
18
1
2019
Statut:
ppublish
Résumé
Laboratory and clinical evidence indicate that continous delivery of levodopa is associated with reduced motor complications compared to standard intermittent levodopa. To assess the pharmacokinetics and efficacy of continuous oral delivery of l-dopa/carbidopa in PD patients with motor fluctuations. 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. 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. 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.
Sections du résumé
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.
Substances chimiques
Antiparkinson Agents
0
Drug Combinations
0
Levodopa
46627O600J
Carbidopa
MNX7R8C5VO
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
425-429Informations de copyright
© 2019 International Parkinson and Movement Disorder Society.