title: Clinical experiences with levodopa methylester (melevodopa) in patients with Parkinson disease experiencing motor fluctuations: an open-label observational study.
abstract: BACKGROUND
  Slow gastric emptying decreasing levodopa (LD) bioavailability contributes to motor fluctuations in Parkinson disease (PD). Melevodopa (LD methylester), ensuring rapid duodenal absorption, has been proposed as rescue therapy for afternoon off periods.
  
  
  OBJECTIVE
  To assess daily motor fluctuations by multiple administrations of Sirio (Chiesi Farmaceutici SpA, Parma, Italy) (melevodopa/carbidopa) in PD patients.
  
  
  METHODS
  In this open-label naturalistic study, 75 PD patients (group A) completely switched standard LD (Sinemet or Madopar) with Sirio at an equivalent dosage (800-1000 mg/d). One hundred nineteen PD patients (group B) partially replaced their standard LD (Sinemet) with Sirio at an equivalent dosage (400-500 mg/d) while continuing Stalevo 100. In both groups, the observational period lasted 6 months. Assessments included an on/off diary, the Unified Parkinson's Disease Rating Scale (motor examination [UPDRS II] and activities of daily living [UPDRS III]), the dyskinesia scale, and an adverse event profile.
  
  
  RESULTS
  Group A showed a significant reduction of afternoon off hours at 6 months (P < 0.05). Forty-five patients (69%) reported a subjective early onset of on motor response. Twelve patients (18.5%) reported its shorter duration. The dyskinesia scale score remained unchanged. Ten patients (13.3%) discontinued melevodopa for gastric intolerance. Group B showed at 6 months a significant reduction of total hours of daily off periods (P < 0.05), particularly in the morning (P < 0.01) and afternoon (P < 0.05). Seventy subjects (59%) expressed positive judgment on quickness of onset of on motor response. The dyskinesia scale score was unchanged. No significant adverse events were reported.
  
  
  CONCLUSIONS
  Switching PD patients with motor fluctuations to melevodopa, particularly in the presence of entacapone, could optimize critical periods of the day such as the morning delay on and afternoon off periods.
authors.affiliation: Parkinson's Disease and Movement Disorders Unit, IRCCS Neurological Institute C. Mondino, Pavia, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Zangaglia
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Stocchi
authors.forename: Massimo
authors.initials: M
authors.lastname: Sciarretta
authors.forename: Angelo
authors.initials: A
authors.lastname: Antonini
authors.forename: Francesca
authors.initials: F
authors.lastname: Mancini
authors.forename: Marco
authors.initials: M
authors.lastname: Guidi
authors.forename: Emilia
authors.initials: E
authors.lastname: Martignoni
authors.forename: Claudio
authors.initials: C
authors.lastname: Pacchetti
mesh_terms: D000368:Aged; D002230:Carbidopa / Q000009:adverse effects / Q000627:therapeutic use*; D002396:Catechols / Q000627:therapeutic use*; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D020820:Dyskinesias / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007980:Levodopa / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D010300:Parkinson Disease / Q000188:drug therapy*; D017060:Patient Satisfaction; D013997:Time Factors
chemical_list: D002396:Catechols; D004338:Drug Combinations; C481098:Stalevo; C009265:carbidopa, levodopa drug combination; C550615:sirio; D007980:Levodopa; D002230:Carbidopa