title: Pharmacokinetics of levodopa/carbidopa microtablets versus levodopa/benserazide and levodopa/carbidopa in healthy volunteers.
abstract: OBJECTIVE
  To compare bioavailability and pharmacokinetics of single doses of 3 different levodopa formulations given orally in healthy volunteers. Two marketed formulations, standard levodopa/carbidopa, 100/25 mg (LC-100), and dispersible levodopa/benserazide, 100/25 mg (LB-100), were used as reference formulations for a newly developed dispersible microtablet formulation of levodopa/carbidopa, 5/1.25 mg (LC-5). The microtablets are intended for individualized dosing of levodopa/carbidopa in Parkinson disease by means of an electronic dose dispenser with a built-in diary for symptom registration.
  
  
  METHODS
  A single-dose, open, randomized, 3-way crossover study was performed in 19 healthy subjects. Concentrations of levodopa, carbidopa, and the metabolite 3-O-MD in plasma were determined after intake of 100 mg of levodopa, that is, one tablet of reference formulations and 20 microtablets of the new formulation.
  
  
  RESULTS
  The LC-5 microtablets were bioequivalent to the LC-100 tablets in area under the curve (AUC) and maximum concentration in plasma (Cmax) for levodopa, and to the LB-100 tablets in AUC. The dispersible levodopa/benserazide formulation showed earlier time to Cmax and significantly higher Cmax for levodopa in plasma compared to the microtablets. Carbidopa showed larger interindividual variation in AUC and Cmax than levodopa, and the bioequivalence comparison LC-5/LC-100 for this compound did not reach the target. Nevertheless, comparison of 3-O-MD levels for LC-5/LC-100, assuming proportionality to levodopa levels, demonstrated bioequivalence.
  
  
  CONCLUSIONS
  The new levodopa/carbidopa microtablets had a pharmacokinetic profile that would allow for a convenient switch of therapy from standard tablets. Frequent dose administration of levodopa/carbidopa microtablets with an electronic dose dispenser might offer an optimal oral drug delivery in Parkinson disease.
authors.affiliation: Department of Neuroscience, Neurology, Uppsala University, SE-75185 Uppsala, Sweden. dag.nyholm@neuro.uu.se
authors.forename: Dag
authors.initials: D
authors.lastname: Nyholm
authors.forename: Tommy
authors.initials: T
authors.lastname: Lewander
authors.forename: Cecilia
authors.initials: C
authors.lastname: Gomes-Trolin
authors.forename: Tobias
authors.initials: T
authors.lastname: Bäckström
authors.forename: Georgios
authors.initials: G
authors.lastname: Panagiotidis
authors.forename: Mats
authors.initials: M
authors.lastname: Ehrnebo
authors.forename: Christer
authors.initials: C
authors.lastname: Nyström
authors.forename: Sten-Magnus
authors.initials: SM
authors.lastname: Aquilonius
mesh_terms: D000328:Adult; D001545:Benserazide / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002230:Carbidopa / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004338:Drug Combinations; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008297:Male; D013607:Tablets; D055815:Young Adult
chemical_list: D004338:Drug Combinations; D013607:Tablets; C005177:benserazide, levodopa drug combination; C009265:carbidopa, levodopa drug combination; D007980:Levodopa; D001545:Benserazide; D002230:Carbidopa