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

Article


Morgan, Michael, Bulmer, Andrew C., Woodruff, Trent M., Proctor, Lavinia M., Williams, Hua M., Stocks, Shelli Z., Pollitt, Sandra, 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. https://doi.org/10.1016/j.ejps.2008.01.009
Article Title

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

ERA Journal ID14755
Article CategoryArticle
AuthorsMorgan, Michael (Author), Bulmer, Andrew C. (Author), Woodruff, Trent M. (Author), Proctor, Lavinia M. (Author), Williams, Hua M. (Author), Stocks, Shelli Z. (Author), Pollitt, Sandra (Author), Taylor, Stephen M. (Author) and Shiels, Ian A. (Author)
Journal TitleEuropean Journal of Pharmaceutical Sciences
Journal Citation33 (4-5), pp. 390-398
Number of Pages9
Year2008
Place of PublicationNetherlands
ISSN0928-0987
1879-0720
Digital Object Identifier (DOI)https://doi.org/10.1016/j.ejps.2008.01.009
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.

KeywordsC5a receptor antagonist; chitosan; enteral administration; peptide absorption; pmx 53; receptor blocking agent
ANZSRC Field of Research 2020321405. Pharmaceutical sciences
340407. Proteins and peptides
320506. Medical biochemistry - proteins and peptides (incl. medical proteomics)
Byline AffiliationsUniversity of Queensland
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