title: Bimodal administration of entacapone in Parkinson's disease patients improves motor control.
abstract: Catechol-O-methyl transferase (COMT) inhibition by entacapone enhances levodopa absorption and reduces 'off' time in Parkinson's disease (PD). We hypothesized that the administration of entacapone in a bimodal fashion (two doses 1 h apart) would enhance levodopa absorption and improve the motor symptoms of PD. Patients with PD (n = 17) were given immediate (IR)- or controlled (CR)-release levodopa each with either one or two doses of entacapone. Bimodal entacapone produced a significant increase in IR and CR levodopa half-life, 'area under the curve' (AUC), and C(max) with levodopa CR. For both IR and CR levodopa, bimodal entacapone resulted in a significant improvement in the Unified Parkinson's Disease Rating Scale part III (motor). Bimodal entacapone increased COMT inhibition, improved the pharmacokinetics of levodopa and improved motor scores for 6 to 8 h. Bimodal use of entacapone may be useful in selected patients to improve motor control and implies that controlled release COMT inhibition would be beneficial in PD patients.
authors.affiliation: Dipartimento di Scienze Medico-Chirurgiche, Università degli Studi di Milano, Via Morandi, San Donato Milanese, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Bet
authors.forename: S R
authors.initials: SR
authors.lastname: Bareggi
authors.forename: F
authors.initials: F
authors.lastname: Pacei
authors.forename: G
authors.initials: G
authors.lastname: Bondiolotti
authors.forename: G
authors.initials: G
authors.lastname: Meola
authors.forename: A H V
authors.initials: AH
authors.lastname: Schapira
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D019540:Area Under Curve; D002394:Catechol O-Methyltransferase; D002396:Catechols / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009069:Movement Disorders / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D009570:Nitriles / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000097:blood / Q000150:complications / Q000188:drug therapy; D012720:Severity of Illness Index
chemical_list: D000978:Antiparkinson Agents; D002396:Catechols; D009570:Nitriles; D007980:Levodopa; C071192:entacapone; D002394:Catechol O-Methyltransferase