Anticoagulant activity of a peptide boronic acid thrombin inhibitor by various routes of administration in rats.

The peptide boronic acid analog Ac-(D)Phe-Pro-boroArg-OH (I) is a potent and selective inhibitor of thrombin. The objective of this study was to determine whether I is active orally or when administered by alternative transmucosal routes. The measured effect was the time for clotting of plasma after initiation with thrombin. With this assay there was a narrow window from no measurable effect to the maximal effect, a clotting time greater than 300 seconds. Intravenous I at a 0.15 mg/kg dose in rats, a nasal 0.45 mg/kg dose, and 3 mg/kg doses administered orally, colonically, or rectally all produced maximal effects. Therefore, although bioavailability cannot be estimated, it is demonstrated that this peptide analog was absorbed by each of these routes.