title: Levodopa/carbidopa microtablets in Parkinson's disease: a study of pharmacokinetics and blinded motor assessment.
abstract: BACKGROUND
  Motor function assessments with rating scales in relation to the pharmacokinetics of levodopa may increase the understanding of how to individualize and fine-tune treatments.
  
  
  OBJECTIVE
  This study aimed to investigate the pharmacokinetic profiles of levodopa-carbidopa and the motor function following a single-dose microtablet administration in Parkinson's disease.
  
  
  METHODS
  This was a single-center, open-label, single-dose study in 19 patients experiencing motor fluctuations. Patients received 150% of their individual levodopa equivalent morning dose in levodopa-carbidopa microtablets. Blood samples were collected at pre-specified time points. Patients were video recorded and motor function was assessed with six UPDRS part III motor items, dyskinesia score, and the treatment response scale (TRS), rated by three blinded movement disorder specialists.
  
  
  RESULTS
  AUC0-4/doseand Cmax/dosefor levodopa was found to be higher in Parkinson's disease patients compared with healthy subjects from a previous study, (p = 0.0008 and p = 0.026, respectively). The mean time to maximum improvement in sum of six UPDRS items score was 78 min (±59) (n = 16), and the mean time to TRS score maximum effect was 54 min (±51) (n = 15). Mean time to onset of dyskinesia was 41 min (±38) (n = 13).
  
  
  CONCLUSIONS
  In the PD population, following levodopa/carbidopa microtablet administration in fasting state, the Cmaxand AUC0-4/dosewere found to be higher compared with results from a previous study in young, healthy subjects. A large between subject variability in response and duration of effect was observed, highlighting the importance of a continuous and individual assessment of motor function in order to optimize treatment effect.
authors.affiliation: Department of Neuroscience, Neurology, Uppsala University, Uppsala, Sweden. marina.senek@neuro.uu.se.
authors.forename: Marina
authors.initials: M
authors.lastname: Senek
authors.affiliation: Department of Neuroscience, Neurology, Uppsala University, Uppsala, Sweden.
authors.forename: Sten-Magnus
authors.initials: SM
authors.lastname: Aquilonius
authors.affiliation: Department of Neuroscience, Neurology, Uppsala University, Uppsala, Sweden.
authors.forename: Håkan
authors.initials: H
authors.lastname: Askmark
authors.affiliation: Department of Pharmacology, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Filip
authors.initials: F
authors.lastname: Bergquist
authors.affiliation: Department of Clinical Neuroscience, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Radu
authors.initials: R
authors.lastname: Constantinescu
authors.affiliation: Acreo Swedish ICT, Kista, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Ericsson
authors.affiliation: Cenvigo, Uppsala, Sweden.
authors.forename: Sara
authors.initials: S
authors.lastname: Lycke
authors.affiliation: Department of Information Technology, Uppsala University, Uppsala, Sweden.
authors.forename: Alexander
authors.initials: A
authors.lastname: Medvedev
authors.affiliation: Computer Engineering, Dalarna University, Falun, Sweden.|Informatics, School of Business, Örebro University, Örebro, Sweden.
authors.forename: Mevludin
authors.initials: M
authors.lastname: Memedi
authors.affiliation: Acreo Swedish ICT, Kista, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Ohlsson
authors.affiliation: Sensidose AB, Sollentuna, Sweden.
authors.forename: Jack
authors.initials: J
authors.lastname: Spira
authors.affiliation: Computer Engineering, Dalarna University, Falun, Sweden.
authors.forename: Jerker
authors.initials: J
authors.lastname: Westin
authors.affiliation: Department of Neuroscience, Neurology, Uppsala University, Uppsala, Sweden.
authors.forename: Dag
authors.initials: D
authors.lastname: Nyholm
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D019540:Area Under Curve; D002230:Carbidopa / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009043:Motor Activity; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology; D013607:Tablets
chemical_list: D000978:Antiparkinson Agents; D013607:Tablets; D007980:Levodopa; D002230:Carbidopa
keywords: Levodopa; Parkinson’s disease; Pharmacodynamics; Pharmacokinetics