Factors associated with motor fluctuations and dyskinesia in Parkinson Disease: potential role of a new melevodopa plus carbidopa formulation (Sirio).

Abstract

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.

• Authors: Fabrizio Stocchi, Stefano Marconi
• Journal: Clinical neuropharmacology (Clin Neuropharmacol) Vol. 33 Issue 4 Pg. 198-203 (Jul 2010) ISSN: 1537-162X [Electronic] United States
• PMID: 20414107 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Antiparkinson Agents
• Delayed-Action Preparations
• Dopamine Agonists
• Drug Combinations
• sirio
• Levodopa
• Carbidopa

Topics

• Antiparkinson Agents (administration & dosage, adverse effects, pharmacokinetics, therapeutic use)
• Biological Availability
• Carbidopa (administration & dosage, adverse effects, pharmacokinetics, therapeutic use)
• Delayed-Action Preparations (administration & dosage, pharmacokinetics, therapeutic use)
• Dopamine Agonists (administration & dosage, adverse effects, pharmacokinetics, therapeutic use)
• Drug Combinations
• Dyskinesia, Drug-Induced (prevention & control)
• Dyskinesias (drug therapy, physiopathology)
• Female
• Humans
• Hyperkinesis (drug therapy, physiopathology)
• Levodopa (administration & dosage, adverse effects, analogs & derivatives, pharmacokinetics, therapeutic use)
• Male
• Parkinson Disease (complications, drug therapy, physiopathology)
• Solubility
• Time Factors