title: Impact of gastric emptying on levodopa pharmacokinetics in Parkinson disease patients.
abstract: Adjunction of the catechol-O-methyltransferase (COMT) inhibitor entacapone (EN) to levodopa/carbidopa (LD/CD) improves motor symptoms in patients with Parkinson disease (PD) by a prolonged elimination of LD. But it is not known whether EN addition influences gastric emptying and thus LD pharmacokinetics and pharmacodynamics. Objectives were to simultaneously determine plasma LD elimination, gastric emptying, and clinical response after a single intake of the same LD dosage as LD/CD--or as (LD/CD/EN) formulation on 2 consecutive days. In both groups, PD patients with delayed gastric emptying had significant lower LD plasma concentrations. Addition of EN did not influence gastric emptying but significantly improved motor response, which was not different for patients with delayed gastric emptying. However, with and without EN adjunction gastric emptying distinctly contributes to the variability of plasma LD bioavailability. This may impact LD delivery to the brain and thus motor response in PD patients. Therefore, fine tuning of LD application, which considers gastric emptying, becomes more and more essential in advanced PD stages with a reduced striatal neuronal dopamine capacity, which is responsible for maintenance of motor response in early PD patients.
authors.affiliation: Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Gudrunstrasse 56, 44791 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: Dirk
authors.initials: D
authors.lastname: Bremen
authors.forename: Wolfgang E
authors.initials: WE
authors.lastname: Schmidt
authors.forename: Siegfried
authors.initials: S
authors.lastname: Muhlack
authors.forename: Dirk
authors.initials: D
authors.lastname: Woitalla
authors.forename: Oliver
authors.initials: O
authors.lastname: Goetze
mesh_terms: D000328:Adult; D000368:Aged; D000978:Antiparkinson Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001682:Biological Availability; D001944:Breath Tests; D002210:Caprylates; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols / Q000494:pharmacology / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005746:Gastric Emptying / Q000502:physiology*; D006801:Humans; D007980:Levodopa / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D016896:Treatment Outcome
chemical_list: D000978:Antiparkinson Agents; D002210:Caprylates; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols; D004791:Enzyme Inhibitors; D009570:Nitriles; D007980:Levodopa; C071192:entacapone; C031492:octanoic acid