title: Inhibition of catechol-O-methyltransferase contributes to more stable levodopa plasma levels.
abstract: 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.
authors.affiliation: Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany. thomas.mueller@ruhr-uni-bochum.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Müller
authors.forename: Christoph
authors.initials: C
authors.lastname: Erdmann
authors.forename: Siegfried
authors.initials: S
authors.lastname: Muhlack
authors.forename: Dirk
authors.initials: D
authors.lastname: Bremen
authors.forename: Horst
authors.initials: H
authors.lastname: Przuntek
authors.forename: Dirk
authors.initials: D
authors.lastname: Woitalla
mesh_terms: D000328:Adult; D000368:Aged; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002230:Carbidopa / Q000097:blood* / Q000627:therapeutic use*; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols / Q000008:administration & dosage / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000097:blood* / Q000627:therapeutic use*; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007980:Levodopa / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D010300:Parkinson Disease / Q000188:drug therapy*
chemical_list: D000978:Antiparkinson Agents; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols; D018491:Dopamine Agonists; D004338:Drug Combinations; D009570:Nitriles; C009265:carbidopa, levodopa drug combination; D007980:Levodopa; C071192:entacapone; D002230:Carbidopa