title: Entacapone enhances the response to levodopa in parkinsonian patients with motor fluctuations. Nomecomt Study Group.
abstract: OBJECTIVE
  To study the effect and safety of entacapone as an adjunct to levodopa treatment in patients with PD with wearing-off motor fluctuations.
  
  
  BACKGROUND
  Entacapone is a catechol-O-methyltransferase (COMT) inhibitor that has been shown to increase the area under the concentration-time curve of plasma levodopa by decreasing its systemic elimination, thereby promoting and improving therapeutic response to it.
  
  
  METHODS
  A total of 171 parkinsonian patients with wearing-off-type motor fluctuations participated in a 6-month randomized, placebo-controlled, double-blind, parallel-group study. The extent of therapeutic response was elicited in the first hand with home diary recordings of "on" and "off" times by the patient and with Unified Parkinson's Disease Rating Scale scoring by the examiner. The patients took either 200 mg entacapone or identical placebos concomitantly with each daily levodopa dose (four to 10 times a day).
  
  
  RESULTS
  Patients' home diaries indicated that entacapone increased the mean (+/- SD) "on" time significantly (9.3 +/- 2.2 to 10.7 +/- 2.2 hours; p < 0.01) and correspondingly decreased the "off" time significantly (5.3 +/- 2.2 to 4.2 +/- 2.2 hours; p < 0.001). The average benefit derived from a daily levodopa dose as related by the patients was increased significantly (p < 0.01). The daily levodopa dose was reduced significantly in the entacapone group, the difference between the groups being 102 mg (p < 0.01). The entacapone-derived increase in the benefit from levodopa was lost almost completely following its withdrawal. Entacapone was well tolerated. Dopaminergic adverse events, which increased, were ameliorated by reducing the levodopa dose. Diarrhea was the most common nondopaminergic adverse event.
  
  
  CONCLUSIONS
  Long-term entacapone treatment effectively prolonged the beneficial response to levodopa in parkinsonian patients with the wearing-off phenomenon. The improvement occurred irrespective of the reduction of the levodopa dose.
authors.affiliation: Department of Neurology, Turku University Hospital, Finland.
authors.forename: U K
authors.initials: UK
authors.lastname: Rinne
authors.forename: J P
authors.initials: JP
authors.lastname: Larsen
authors.forename: A
authors.initials: A
authors.lastname: Siden
authors.forename: J
authors.initials: J
authors.lastname: Worm-Petersen
mesh_terms: D000978:Antiparkinson Agents / Q000627:therapeutic use*; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009043:Motor Activity; D009570:Nitriles; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology*
chemical_list: D000978:Antiparkinson Agents; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols; D004791:Enzyme Inhibitors; D009570:Nitriles; D007980:Levodopa; C071192:entacapone