title: Frequent administration of levodopa/carbidopa microtablets vs levodopa/carbidopa/entacapone in healthy volunteers.
abstract: OBJECTIVE
  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).
  
  
  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.
authors: Department of Neuroscience, Neurology, Uppsala University, Sweden. dag.nyholm@neuro.uu.se
authors: D
authors: D
authors: Nyholm
authors: M
authors: M
authors: Ehrnebo
authors: T
authors: T
authors: Lewander
authors: C G
authors: CG
authors: Trolin
authors: T
authors: T
authors: Bäckström
authors: G
authors: G
authors: Panagiotidis
authors: J
authors: J
authors: Spira
authors: C
authors: C
authors: Nyström
authors: S-M
authors: SM
authors: Aquilonius
mesh_terms: D000328:Adult; D002230:Carbidopa / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002396:Catechols / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D009570:Nitriles / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013607:Tablets; D055815:Young Adult
chemical_list: D002396:Catechols; D004338:Drug Combinations; D009570:Nitriles; D013607:Tablets; D007980:Levodopa; C071192:entacapone; D002230:Carbidopa