title: The levodopa wearing-off phenomenon in Parkinson's disease: pharmacokinetic considerations.
abstract: Levodopa is the most efficacious treatment in the management of Parkinson's disease. Unfortunately, chronic use of traditional levodopa/dopa decarboxylase inhibitor formulations is associated with the development of complications, such as wearing-off and dyskinesia. In an attempt to avoid these complications, some physicians delay the introduction of levodopa or employ levodopa-sparing strategies; however, these strategies are frequently suboptimal for patients. As most patients require the superior efficacy of levodopa during the course of their disease, an appreciation of the changing response to levodopa over time and an understanding of the pharmacokinetic principles underlying the development of complications such as wearing-off is essential in the long-term management of the patient.
authors.affiliation: Department of Neurology, IRCCS San Raffaele Pisana, Via della Pisana 235, 00163, Rome, Italy. Fabrizio.stocchi@sanraffaele.it
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Stocchi
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D002230:Carbidopa / Q000008:administration & dosage / Q000627:therapeutic use; D002394:Catechol O-Methyltransferase / Q000378:metabolism; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols / Q000008:administration & dosage / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003692:Delayed-Action Preparations; D004296:Dopa Decarboxylase / Q000378:metabolism; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004361:Drug Tolerance; D004409:Dyskinesia, Drug-Induced / Q000209:etiology; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D009570:Nitriles / Q000008:administration & dosage / Q000627:therapeutic use; D010300:Parkinson Disease / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism*
chemical_list: D000978:Antiparkinson Agents; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols; D003692:Delayed-Action Preparations; D004791:Enzyme Inhibitors; D009570:Nitriles; D007980:Levodopa; C071192:entacapone; D002394:Catechol O-Methyltransferase; D004296:Dopa Decarboxylase; D002230:Carbidopa