Inhibition of catechol-O-methyltransferase contributes to more stable levodopa plasma levels

• Published in: Movement disorders Vol. 21; no. 3; pp. 332 - 336
• Main Authors: Müller, Thomas, Erdmann, Christoph, Muhlack, Siegfried, Bremen, Dirk, Przuntek, Horst, Woitalla, Dirk
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-03-2006; Wiley
• Subjects: Adult; Aged; Antiparkinson Agents - administration & dosage; Antiparkinson Agents - pharmacology; Biological and medical sciences; Carbidopa - blood; Carbidopa - therapeutic use; Catechol O-Methyltransferase Inhibitors; Catechols - administration & dosage; Catechols - pharmacology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dopamine Agonists - blood; Dopamine Agonists - therapeutic use; Drug Combinations; Drug Therapy, Combination; Drug toxicity and drugs side effects treatment; entacapone; Female; Humans; levodopa; Levodopa - blood; Levodopa - pharmacology; Levodopa - therapeutic use; Male; Medical sciences; Middle Aged; Neurology; Nitriles; Parkinson Disease - drug therapy; Parkinson's disease; Pharmacology. Drug treatments; Toxicity: nervous system and muscle; Nervous system diseases; Parkinson's disease; Enzyme; Transferases; Parkinson disease; Catechol O-methyltransferase; Cerebral disorder; Methyltransferases; Central nervous system disease; Entacapone; Degenerative disease; Levodopa; Extrapyramidal syndrome
• ISSN: 0885-3185; 1531-8257
• DOI: 10.1002/mds.20717

The short plasma half‐life limits the antiparkinsonian efficacy of levodopa/carbidopa (LD/CD). Administration of LD/CD with the catechol‐O‐methyltransferase inhibitor entacapone in one tablet (LCE) may extend plasma half‐life of LD and thus its effect on motor symptoms in patients with Parkinson's disease (PD). The objectives of this study were to monitor the motor response to a switch from LD/CD to LCE by a simultaneous performance of an instrumental motor test and rating of motor symptoms and to compare the LD plasma behavior between both conditions in terms of stability. Twenty‐one treated PD patients received LD/CD and then the identical oral LD dosage of LCE within a standardized setting on 2 consecutive days. Rating better reflected the motor improvement after LD application than the instrumental test. Motor symptoms of PD patients decreased significantly more during the LCE than the LD/CD condition, probably due to significantly higher LD plasma levels and a significantly less pronounced fall of the LD concentrations following the second LD intake. Our study shows a more stable LD plasma behavior during LCE intake and accordingly a better effect on motor symptoms according to rating outcomes and motor test results to a lesser extent. © 2005 Movement Disorder Society