Oral activity of peptide bradykinin antagonists following intragastric administration in the rat.

This study has investigated the oral activity, following intragastric administration, of three potent and long-acting peptide-based bradykinin antagonists, HOE-140, B9430, and CP-0597, in the anesthetized rat, using bradykinin-induced hypotension. Two of the three bradykinin antagonists, B9430 and HOE-140, but not CP-0597, were found to be active following intragastric administration, producing dose-dependent (1, 3, and 10 mg/kg) and selective inhibition of bradykinin-induced hypotension. At a dose of 10 mg/kg, the inhibition of bradykinin-induced hypotension occurred within 15 min and lasted for at least 2 h, which was the duration of the experiment. HOE-140 and CP-0597, 10 micrograms/kg i.v., produced significant inhibition of bradykinin-induced responses that lasted for 60 min. B9430, 10 micrograms/kg i.v., produced a significantly greater inhibition than HOE-140 and CP-0597, this inhibition being significant for the duration of the experiment (2 h) compared with saline controls. Considering the close chemical structure of CP-0597 compared with HOE-140 and B9430, it is not clear as to why CP-0597 was inactive via the intragastric route. This is the first demonstration of the oral activity of peptide-based bradykinin antagonists following intragastric administration in the rat.
AuthorsE T Whalley, W L Hanson, J M Stewart, L Gera
JournalCanadian journal of physiology and pharmacology (Can J Physiol Pharmacol) Vol. 75 Issue 6 Pg. 629-32 (Jun 1997) ISSN: 0008-4212 [Print] CANADA
PMID9276140 (Publication Type: Journal Article)
Chemical References
  • CP 0597
  • Oligopeptides
  • icatibant
  • Bradykinin
  • Administration, Oral
  • Animals
  • Biological Availability
  • Bradykinin (analogs & derivatives, antagonists & inhibitors, pharmacokinetics, pharmacology)
  • Dose-Response Relationship, Drug
  • Hypotension (chemically induced)
  • Male
  • Oligopeptides (pharmacokinetics, pharmacology)
  • Rats
  • Rats, Sprague-Dawley

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