Frequent administration of levodopa/carbidopa microtablets vs levodopa/carbidopa/entacapone in healthy volunteers

Acta Neurol Scand. 2013 Feb;127(2):124-32. doi: 10.1111/j.1600-0404.2012.01700.x. Epub 2012 Jul 4.


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.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Carbidopa / administration & dosage
  • Carbidopa / blood
  • Carbidopa / pharmacokinetics*
  • Catechols / administration & dosage
  • Catechols / blood
  • Catechols / pharmacokinetics*
  • Cross-Over Studies
  • Drug Combinations
  • Female
  • Humans
  • Levodopa / administration & dosage
  • Levodopa / blood
  • Levodopa / pharmacokinetics*
  • Male
  • Nitriles / administration & dosage
  • Nitriles / blood
  • Nitriles / pharmacokinetics*
  • Tablets
  • Young Adult


  • Catechols
  • Drug Combinations
  • Nitriles
  • Tablets
  • Levodopa
  • entacapone
  • Carbidopa