Pharmacokinetics of a C5a receptor antagonist in the rat after different sites of enteral administration

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Title Pharmacokinetics of a C5a receptor antagonist in the rat after different sites of enteral administration
Author Morgan, Michael; Bulmer, Andrew Cameron; Woodruff, Trent M.; Proctor, Lavinia M.; Williams, Hua M.; Stocks, Shelli Z.; Taylor, Stephen M.; Shiels, Ian A.
Journal Name European Journal of Pharmaceutical Sciences
Year Published 2008
Place of publication Netherlands
Publisher Elsevier BV
Abstract Pharmacokinetics of the orally active, cyclic peptide complement factor C5a receptor antagonist, AcF-[OP(d-Cha)WR] (PMX53) were determined in the rat. Biliary excretion of the unchanged drug was a major route of elimination after intravenous administration, but not following oral administration. Portal and peripheral blood levels of PMX53 were determined after oral administration or direct injection into the ileum, colon or local administration into the rectum. PMX53 was rapidly absorbed from mucosal sites, with peak plasma levels occurring as early as 5 min post-administration. Early portal blood levels were consistently higher than peripheral levels following ileal, colonic and rectal administration, but not after oral dosing. The results suggest that hepatic elimination occurs rapidly with higher (≥100 ng/ml) peripheral blood levels of the drug. Combination of PMX53 with the excipient chitosan resulted in significantly higher peripheral levels of the drug following ileal and colonic application, but not with buccal or oral administration. Buccal administration resulted in a similar plasma pharmacokinetic profile to oral administration. These results suggest that PMX53 is rapidly absorbed across mucosal membranes in the rat, and that administration using excipients such as chitosan may offer a method of increasing bioavailability.
Peer Reviewed Yes
Published Yes
Publisher URI http://www.elsevier.com/wps/find/journaldescription.cws_home/523997/description#description
Alternative URI http://dx.doi.org/10.1016/j.ejps.2008.01.009
Volume 33
Issue Number 4-5
Page from 390
Page to 398
ISSN 0928-0987
Date Accessioned 2009-11-05
Language en_AU
Research Centre Heart Foundation Research Centre; Griffith Health Institute
Faculty Griffith Health Faculty
Subject PRE2009-Biological and Medical Chemistry
URI http://hdl.handle.net/10072/27410
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1x

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