title: Levodopa infusion combined with entacapone or tolcapone in Parkinson disease: a pilot trial.
abstract: OBJECTIVE
  Catechol-O-methyltransferase inhibitors may be used to decrease levodopa requirement. The objective was to investigate whether the levodopa/carbidopa intestinal gel infusion dose can be reduced by 20% without worsening of motor fluctuations and levodopa concentration stability when oral catechol-O-methyltransferase inhibitors are added.
  
  
  METHODS
  A short-term, randomized, partly blinded, crossover, investigator-initiated clinical trial was performed, with levodopa/carbidopa intestinal gel combined with oral entacapone and tolcapone on two different days in 10 patients. The primary outcome measure was difference in coefficient of variation of levodopa in plasma between levodopa/carbidopa, levodopa/carbidopa/entacapone, and levodopa/carbidopa/tolcapone. The secondary outcome measures other pharmacokinetic variables, patient-reported outcome, and blinded analysis of motor performance.
  
  
  RESULTS
  Variation of plasma levodopa concentrations did not differ significantly between the treatments. The treatments did not differ regarding motor performance. Levodopa concentrations were significantly higher using tolcapone. Concentrations of the metabolite 3-O-methyldopa decreased gradually during catechol-O-methyltransferase inhibition.
  
  
  CONCLUSIONS
  According to this small, short-term pilot study, oral catechol-O-methyltransferase inhibitors administered in 5-h intervals may be useful in cases where levodopa/carbidopa intestinal gel dose reduction is wanted. Stability of plasma levodopa levels is not significantly altered, and off-time is not increased when decreasing the levodopa/carbidopa intestinal gel dose by 20%. Rather, the dose should probably be decreased more than 20%, especially under tolcapone co-treatment, to avoid increased dyskinesias with time.
authors.affiliation: Department of Neuroscience, Uppsala Department of Pharmacy, Uppsala University, Uppsala, Sweden. dag.nyholm@neuro.uu.se
authors.forename: D
authors.initials: D
authors.lastname: Nyholm
authors.forename: A
authors.initials: A
authors.lastname: Johansson
authors.forename: H
authors.initials: H
authors.lastname: Lennernäs
authors.forename: H
authors.initials: H
authors.lastname: Askmark
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D001577:Benzophenones / Q000627:therapeutic use; D002396:Catechols / Q000627:therapeutic use; D018592:Cross-Over Studies; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000627:therapeutic use; D009596:Nitrophenols / Q000627:therapeutic use; D010300:Parkinson Disease / Q000188:drug therapy*; D010865:Pilot Projects; D057566:Self Report; D016037:Single-Blind Method; D013548:Sweden; D000077867:Tolcapone; D014443:Tyrosine / Q000031:analogs & derivatives / Q000097:blood
chemical_list: D000978:Antiparkinson Agents; D001577:Benzophenones; D002396:Catechols; D009570:Nitriles; D009596:Nitrophenols; D014443:Tyrosine; D007980:Levodopa; C071192:entacapone; D000077867:Tolcapone; C008404:3-methoxytyrosine