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

Morgan, Michael and Bulmer, Andrew C. and Woodruff, Trent M. and Proctor, Lavinia M. and Williams, Hua M. and Stocks, Shelli Z. and Pollitt, Sandra and Taylor, Stephen M. and Shiels, Ian A. (2008) Pharmacokinetics of a C5a receptor antagonist in the rat after different sites of enteral administration. European Journal of Pharmaceutical Sciences, 33 (4-5). pp. 390-398. ISSN 0928-0987


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.

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Item Type: Article (Commonwealth Reporting Category C)
Refereed: Yes
Item Status: Live Archive
Faculty / Department / School: Historic - Faculty of Sciences - Department of Biological and Physical Sciences
Date Deposited: 05 May 2010 12:50
Last Modified: 04 Aug 2014 19:38
Uncontrolled Keywords: C5a receptor antagonist; chitosan; enteral administration; peptide absorption; pmx 53; receptor blocking agent
Fields of Research : 11 Medical and Health Sciences > 1115 Pharmacology and Pharmaceutical Sciences > 111504 Pharmaceutical Sciences
03 Chemical Sciences > 0304 Medicinal and Biomolecular Chemistry > 030406 Proteins and Peptides
11 Medical and Health Sciences > 1101 Medical Biochemistry and Metabolomics > 110106 Medical Biochemistry: Proteins and Peptides (incl. Medical Proteomics)
Socio-Economic Objective: E Expanding Knowledge > 97 Expanding Knowledge > 970111 Expanding Knowledge in the Medical and Health Sciences
Identification Number or DOI: 10.1016/j.ejps.2008.01.009

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