DSpace

King Saud University Repository >
King Saud University >
COLLEGES >
Health Colleges >
College of Pharmacy >
College of Pharmacy >

Please use this identifier to cite or link to this item: http://hdl.handle.net/123456789/16968

Title: Disposition of abouthiouzine: A novel antihyperthyroid drug
Authors: (Alkharfy, Khalid M.),
Keywords: abouthiouzine; pharmacokinetics; rabbits; dogs; intravenous; oral
Issue Date: 2007
Publisher: JOHN WILEY & SONS LTD, THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
Abstract: Abouthiouzine is a novel antithyroid agent with a profile of fewer reported adverse effects than other currently used drugs. The purpose of this current work was to explore, for the first time, the disposition of abouthiouzine following intravenous and oral administration using an animal model; also, to study its plasma protein binding properties. Abouthiouzine (2 mg/kg intravenously) was administered to healthy male Vole rabbits and Beagle dogs. A dose of 20 mg/kg of the drug was also given orally to another group of Beagle dogs. Abouthiouzine plasma concentrations were measured using an HPLC method, and its pharmacokinetic parameters were determined by non-compartmental analysis. Abouthiouzine plasma protein binding was determined using an ultrafiltration technique. The drug was quickly eliminated from the rabbit and dog systemic circulations with terminal half-lives (T-1/2 lambda) of 0.7h and 1.9h, respectively. The calculated T-1/2 lambda following the oral administration in dogs was 1.8 h. Total abouthiouzine clearance (CL) in rabbits was 7.84 +/- 0.87 ml/min/kg, and 4.03 +/- 0.83 ml/min/kg in dogs. The apparent volume of distribution at steady state (V-ss) in rabbits and dogs was 360.09 +/- 63.41 ml/kg and 481.10 +/- 62.64 ml/kg, respectively. The absolute oral bioavailability in dogs was similar to 16%, which may indicate poor absorption characteristics of the pure drug and/or an extensive first past effect. Protein binding studies have demonstrated that abouthiouzine has moderate-to-high binding properties (similar to 63%-86%). Further studies are needed to evaluate the route of elimination of abouthiouzine in these animal models including any metabolite formation and the role of enterohepatic recycling in this process. Copyright (c) 2007 John Wiley & Sons, Ltd.
URI: http://hdl.handle.net/123456789/16968
Appears in Collections:College of Pharmacy

Files in This Item:

File Description SizeFormat
6.doc62.5 kBMicrosoft WordView/Open

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

 

DSpace Software Copyright © 2002-2007 MIT and Hewlett-Packard - Feedback