ArticleEuropean journal of clinical pharmacology2018
Population pharmacokinetics of levodopa/carbidopa microtablets in healthy subjects and Parkinson's disease patients.
Article in European journal of clinical pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- A computational pharmacokinetic-pharmacodynamic framework for simulating and comparing individualized levodopa dosing in Parkinson's disease.Frontiers in pharmacology · 2026Article
- Pharmacokinetic Model-Based Control across the Blood-Brain Barrier for Circadian Entrainment.International journal of molecular sciences · 2023Article
- Model-based optimization of controlled release formulation of levodopa for Parkinson's disease.Scientific reports · 2023Article
- Clinical Pharmacology of Entacapone (Comtan) From the FDA Reviewer.The international journal of neuropsychopharmacology · 2022Article
- Personalized Medicine Approach in Treating Parkinson's Disease, Using Oral Administration of Levodopa/Carbidopa Microtablets in Clinical Practice.Journal of personalized medicine · 2021Article
- An integrative model of Parkinson's disease treatment including levodopa pharmacokinetics, dopamine kinetics, basal ganglia neurotransmission and motor action throughout disease progression.Journal of pharmacokinetics and pharmacodynamics · 2021Article
Corrections and comments
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesLow dose, dispersible, levodopa/carbidopa microtablets with an automatic dose dispenser have been developed to facilitate individualized levodopa treatment. The aim of this study was to characterize the pharmacokinetics (PK) of levodopa and carbidopa after microtablet administration, and evaluate the impact of potential covariates.
methodsThe population PK analysis involved data from 18 healthy subjects and 18 Parkinson's disease patients included in two single-dose, open-label levodopa/carbidopa microtablet studies. The analysis was carried out using non-linear mixed effects modeling. Bodyweight was included on all disposition parameters according to allometric scaling. Potential influence of additional covariates was investigated using graphical evaluation and adjusted adaptive least absolute shrinkage and selection operator.
resultsDispositions of levodopa and carbidopa were best described by a two- and one-compartment model respectively. Double-peak profiles were described using two parallel absorption compartments. Levodopa apparent clearance was found to decrease with increasing carbidopa dose (15% lower with 75 compared to 50 mg of carbidopa) and disease stage (by 18% for Hoehn and Yahr 1 to 4). Carbidopa apparent clearance was found to decrease with age (28% between the age of 60 and 80 years). An external evaluation showed the model to be able to reasonably well predict levodopa concentrations following multiple-dose microtablet administration in healthy subjects.
conclusionsThe presented models adequately described the PK of levodopa and carbidopa, following microtablet administration. The developed model may in the future be combined with a pharmacokinetic-pharmacodynamic target and used for individualized dose selection, utilizing the flexibility offered by the microtablets.
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