title: Entacapone prolongs levodopa response in a one month double blind study in parkinsonian patients with levodopa related fluctuations.
abstract: OBJECTIVE
  To establish, in a double blind manner, the antiparkinsonian effects of repeated dosing with entacapone, a peripheral COMT inhibitor.
  
  
  METHODS
  A one month, cross over study was conducted. During the two four-week treatment periods, entacapone (200 mg) or placebo was given with each levodopa dose four to 10 times daily. Motor responses were repeatedly quantified using the motor part of UPDRS. Plasma levodopa and its metabolites were measured.
  
  
  RESULTS
  Entacapone prolonged the availability of levodopa in the plasma and thus to the brain by decreasing its peripheral O-methylation and slowing its elimination rate, without affecting the maximum plasma levodopa concentration or the time to maximum concentration. Corresponding with the pharmacokinetic findings, entacapone prolonged the duration of motor response to an individual levodopa/DDC inhibitor dose by 34 minutes (24%, P = 0.001) and dyskinesiae by 39 minutes (37%, P = 0.002) compared with placebo, without affecting their magnitude or starting time. Entacapone treatment resulted in a reduction of 16% in the mean total daily levodopa dose due to dyskinesiae. Also, according to the home diaries, the mean daily "on" time increased by 2.1 hours compared with placebo, despite the lowered mean levodopa intake.
  
  
  CONCLUSIONS
  The efficacy of repeated entacapone dosing as an adjuvant to levodopa/DDC inhibitor treatment for Parkinson's disease with levodopa related fluctuations is verified.
authors.affiliation: Department of Neurology, University of Turku, Finland.
authors.forename: H M
authors.initials: HM
authors.lastname: Ruottinen
authors.forename: U K
authors.initials: UK
authors.lastname: Rinne
mesh_terms: D000368:Aged; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D001682:Biological Availability; D002396:Catechols / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D016903:Drug Monitoring; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use*; D008875:Middle Aged; D009043:Motor Activity; D009570:Nitriles; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D000978:Antiparkinson Agents; D002396:Catechols; D004791:Enzyme Inhibitors; D009570:Nitriles; D007980:Levodopa; C071192:entacapone