Pharmacokinetics of a C5a receptor antagonist in the rat after different sites of enteral administration
Article
Article Title | Pharmacokinetics of a C5a receptor antagonist in the rat after different sites of enteral administration |
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ERA Journal ID | 14755 |
Article Category | Article |
Authors | Morgan, 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 Title | European Journal of Pharmaceutical Sciences |
Journal Citation | 33 (4-5), pp. 390-398 |
Number of Pages | 9 |
Year | 2008 |
Place of Publication | Netherlands |
ISSN | 0928-0987 |
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. |
Keywords | C5a receptor antagonist; chitosan; enteral administration; peptide absorption; pmx 53; receptor blocking agent |
ANZSRC Field of Research 2020 | 321405. Pharmaceutical sciences |
340407. Proteins and peptides | |
320506. Medical biochemistry - proteins and peptides (incl. medical proteomics) | |
Byline Affiliations | University of Queensland |
https://research.usq.edu.au/item/9zx20/pharmacokinetics-of-a-c5a-receptor-antagonist-in-the-rat-after-different-sites-of-enteral-administration
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