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

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: 390-398. doi:10.1016/j.ejps.2008.01.009

Author Morgan, Michael
Bulmer, Andrew C.
Woodruff, Trent M.
Proctor, Lavinia M.
Williams, Hua M.
Stocks, Shelli Z.
Pollitt, Sandra
Taylor, Stephen M.
Shiels, Ian A
Title Pharmacokinetics of a C5a receptor antagonist in the rat after different sites of enteral administration
Journal name European Journal of Pharmaceutical Sciences   Check publisher's open access policy
ISSN 0928-0987
Publication date 2008-04-23
Year available 2008
Sub-type Article (original research)
DOI 10.1016/j.ejps.2008.01.009
Volume 33
Issue 4-5
Start page 390
End page 398
Total pages 9
Place of publication Amsterdam, The Netherlands
Publisher Elsevier Science
Language eng
Subject C1
060804 Animal Immunology
730100 Clinical (Organs, Diseases and Abnormal Conditions)
1115 Pharmacology and Pharmaceutical Sciences
Formatted 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.
© 2008 Elsevier B.V. All rights reserved.

Keyword Enteral Administration
C5a Receptor Antagonist
Peptide Absorbtion
Q-Index Code C1
Q-Index Status Confirmed Code

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Created: Wed, 30 Jul 2008, 02:21:14 EST