title: Novel levodopa gastroretentive dosage form: in-vivo evaluation in dogs.
abstract: Due to its narrow absorption window, levodopa has to be administered continuously to the upper parts of the intestine in order to maintain sustained therapeutic levels. This may be achieved by a controlled release (CR) gastroretentive dosage form (GRDF). The aim of this work was to develop a novel GRDF, based on unfolding polymeric membranes, that combines extended dimensions with high rigidity, and to examine the pharmacokinetics of levodopa compounded in the GRDF. Levodopa CR-GRDFs were administered to beagle dogs pretreated with carbidopa. The CR-GRDF location in the gastrointestinal tract was determined by X-ray, and serial blood samples were collected and assayed for levodopa. Optimization of the pharmacokinetic profile of levodopa from the CR-GRDFs was carried out based on the in-vitro in-vivo correlation following modifications of the release rates (adjusted by various membrane thicknesses) and drug loads. The successful CR-GRDF maintained therapeutic levodopa concentrations (>500 ng ml(-1)) over 9 h. In comparison to non-gastroretentive CR-particles and oral solution, mean absorption time was significantly extended. These outcomes demonstrate that the CR-GRDF may be used to improve levodopa therapy and can be applied to extend the absorption of other narrow absorption window drugs that require continuous input.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, POB 12065, Jerusalem 91120, Israel.
authors.forename: Eytan A
authors.initials: EA
authors.lastname: Klausner
authors.forename: Sara
authors.initials: S
authors.lastname: Eyal
authors.forename: Eran
authors.initials: E
authors.lastname: Lavy
authors.forename: Michael
authors.initials: M
authors.lastname: Friedman
authors.forename: Amnon
authors.initials: A
authors.lastname: Hoffman
mesh_terms: D000284:Administration, Oral; D000465:Algorithms; D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations; D004285:Dogs; D004339:Drug Compounding; D005753:Gastric Mucosa / Q000378:metabolism*; D006207:Half-Life; D007275:Injections, Intravenous; D007980:Levodopa / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019999:Pharmaceutical Solutions; D011859:Radiography; D012995:Solubility; D013270:Stomach / Q000000981:diagnostic imaging
chemical_list: D000978:Antiparkinson Agents; D003692:Delayed-Action Preparations; D019999:Pharmaceutical Solutions; D007980:Levodopa