title: Complexity of motor response to different doses of duodenal levodopa infusion in Parkinson disease.
abstract: OBJECTIVE
  The aim was to elaborately describe individual pharmacokinetic-pharmacodynamic profiles in patients with difficult-to-treat dyskinesias treated with levodopa/carbidopa intestinal gel infusion.
  
  
  METHODS
  A nonrandomized, partly blinded, investigator-initiated trial was conducted in 5 patients with idiopathic Parkinson disease who were difficult to keep in "on" state without dyskinesia. Levodopa/carbidopa intestinal gel (Duodopa) doses of 80% to 120% of individually and clinically optimized dosage were infused during five 4-hour periods. Pharmacokinetic profiling, blinded assessment of video recordings, and objective movement analysis were applied every 20 to 30 minutes.
  
  
  RESULTS
  Individual correlations between plasma levodopa concentrations and corresponding motor scores 20 to 30 minutes after the sampling time were significant in all patients (P < 0.05 and P < 0.001). Motor scores were generally stable during the 4-hour periods. The objective test revealed that motor performance was faster the more dyskinetic the patients were. Mean individual Treatment Response Scale scores were positive in 24 of the 25 steady-state periods. Dystonia was always combined with choreic dyskinesias.
  
  
  CONCLUSIONS
  Motor response from different doses of levodopa/carbidopa intestinal gel is in a broad sense predictable even in dyskinetic patients although major interindividual differences in dose requirement, plasma levels, and motor response are found. That motor performance was faster the more dyskinetic the patients were implies that motor performance may be better with moderate dyskinesia than with mild dyskinesia. This may explain why patients with persistent dyskinesias choose to keep their doses above the dyskinesia threshold. There is no ideal therapeutic window in such patients, but levodopa infusion offers stable motor response.
authors.affiliation: Department of Neuroscience, Neurology, Uppsala University, E-75185 Uppsala, Sweden. dag.nyholm@neuro.uu.se
authors.forename: Dag
authors.initials: D
authors.lastname: Nyholm
authors.forename: Anders
authors.initials: A
authors.lastname: Johansson
authors.forename: Sten-Magnus
authors.initials: SM
authors.lastname: Aquilonius
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Hellquist
authors.forename: Hans
authors.initials: H
authors.lastname: Lennernäs
authors.forename: Håkan
authors.initials: H
authors.lastname: Askmark
mesh_terms: D000368:Aged; D000978:Antiparkinson Agents / Q000097:blood / Q000627:therapeutic use*; D002230:Carbidopa / Q000097:blood / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004359:Drug Therapy, Combination; D004386:Duodenum; D004409:Dyskinesia, Drug-Induced / Q000209:etiology; D005260:Female; D006801:Humans; D007980:Levodopa / Q000097:blood / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009068:Movement / Q000187:drug effects*; D010300:Parkinson Disease / Q000188:drug therapy; D012720:Severity of Illness Index; D014741:Video Recording
chemical_list: D000978:Antiparkinson Agents; D007980:Levodopa; D002230:Carbidopa