Clinical experiences with levodopa methylester (melevodopa) in patients with Parkinson disease experiencing motor fluctuations: an open-label observational study.
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.
Zangaglia
Roberta
R
Parkinson's Disease and Movement Disorders Unit, IRCCS Neurological Institute C. Mondino, Pavia, Italy.
Stocchi
Fabrizio
F
Sciarretta
Massimo
M
Antonini
Angelo
A
Mancini
Francesca
F
Guidi
Marco
M
Martignoni
Emilia
E
Pacchetti
Claudio
C
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
D002396:Catechols; D004338:Drug Combinations; C481098:Stalevo; C009265:carbidopa, levodopa drug combination; C550615:sirio; D007980:Levodopa; D002230:Carbidopa