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Frequent administration of levodopa/carbidopa microtablets vs levodopa/carbidopa/entacapone in healthy volunteers
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
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2013 (English)In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 127, no 2, 124-132 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES:

An oral dispersible microtablet formulation of levodopa/carbidopa 5/1.25 mg (LC-5) was developed for individualized repeated dosing. The aim was to compare pharmacokinetic profiles of LC-5 and levodopa/carbidopa/entacapone (LCE).

MATERIALS AND METHODS:

A randomized, crossover study was carried out in 11 healthy subjects. Plasma concentrations of levodopa, carbidopa and 3-O-methyldopa were determined after intake of 300 mg levodopa during the day, either as three intakes of 100/25/200 mg LCE or as a morning dose of 75/18.25 mg followed by five repeated doses of 45/11.25 mg LC-5.

RESULTS:

Repeated dosing (2.4-hourly) with LC-5 microtablets compared to LCE (6-hourly) avoided long periods with low plasma levodopa levels. Time to maximum plasma concentrations was significantly shorter for LC-5. LC-5 showed lower fluctuation index (FI) in plasma compared to LCE (ANOVA P = 0.0028). FI for dose 2-5 was on average 1.26 for levodopa in LC-5, and 2.23 for dose 1-2 of LCE. The ratio between the two mean FI:s is 0.565; that is, LC-5 gave nearly half the FI as compared to LCE.

CONCLUSIONS:

Fractionation of levodopa with LC-5 into small, frequent administrations as compared to standard administrations of LCE decreased the FI in plasma for both levodopa and carbidopa by nearly half.

Place, publisher, year, edition, pages
2013. Vol. 127, no 2, 124-132 p.
National Category
Neurology
Research subject
Neurology
Identifiers
URN: urn:nbn:se:uu:diva-188647DOI: 10.1111/j.1600-0404.2012.01700.xISI: 000313886700009PubMedID: 22762460OAI: oai:DiVA.org:uu-188647DiVA: diva2:578502
Available from: 2012-12-18 Created: 2012-12-18 Last updated: 2017-12-06Bibliographically approved

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Nyholm, DagLewander, TommyAquilonius, Sten-Magnus

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