Factors associated with motor fluctuations and dyskinesia in Parkinson Disease: potential role of a new melevodopa plus carbidopa formulation (Sirio).
Parkinson disease is a progressive movement disorder caused by loss of dopaminergic neurons in the substantia nigra. Of unknown etiology, Parkinson disease is characterized by 4 cardinal symptoms: tremor at rest, bradykinesia, postural instability, and rigidity. The current criterion-standard drug used in the management of parkinsonian symptoms is levodopa (l-dopa). However, long-term l-dopa therapy is associated with the development of motor complications; approximately 50% to 80% of patients will develop motor complications within 5 to 10 years of l-dopa treatment initiation. Motor complications can be divided into motor fluctuations, caused largely through pulsatile dopamine stimulation and low l-dopa concentrations, and dyskinesia, associated more often with peak l-dopa concentrations. Ultimately, the main goal was to provide steady l-dopa concentrations, without peaks and troughs. Empirical investigations using parenteral infusions of l-dopa and highly soluble l-dopa prodrugs have shown that there is benefit in ameliorating the peaks and troughs associated with traditional oral l-dopa formulations. Recently, the development of highly soluble oral l-dopa prodrugs has facilitated rapid, regular, and reliable l-dopa availability. This review evaluates some of the pharmacologic strategies in the management of motor complications in Parkinson disease and therapy optimization, with a focus on the use of CHF 1512 (Sirio), a combination of melevodopa (l-dopa methylester, a highly soluble prodrug of l-dopa) plus carbidopa in an effervescent tablet formulation.
Stocchi
Fabrizio
F
IRCCS San Raffaele Pisana, Rome; and daggerMedical Department, Chiesi Farmaceutici S.p.A., Parma, Italy. stocchi@sanraffaele.it
Marconi
Stefano
S
D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001682:Biological Availability; D002230:Carbidopa / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004338:Drug Combinations; D004409:Dyskinesia, Drug-Induced / Q000517:prevention & control*; D020820:Dyskinesias / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D006801:Humans; D006948:Hyperkinesis / Q000188:drug therapy* / Q000503:physiopathology; D007980:Levodopa / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D008297:Male; D010300:Parkinson Disease / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D012995:Solubility; D013997:Time Factors
D000978:Antiparkinson Agents; D003692:Delayed-Action Preparations; D018491:Dopamine Agonists; D004338:Drug Combinations; C550615:sirio; D007980:Levodopa; D002230:Carbidopa