Intranasal Absorption of the Platelet Glycoprotein IIb/IIIa Receptor Antagonist, DMP 755, and the Effect of Anesthesia on Nasal Bioavailability

Abstract

□ Intranasal absorption and bioavailability of DMP 755, a peptidomimetic, platelet glycoprotein IIb/IIIa receptor antagonist, were examined in anesthetized and lightly sedated dogs. Nasal bioavailability was determined by measuring plasma concentrations relative to those after intravenous dosing. DMP 755 is an ester prodrug, and bioavailability reflects concentrations of the acid hydrolysis product. Nasal bioavailability in dogs anesthetized with pentobarbital was 85±4%, whereas in dogs anesthetized with the short-acting anesthetic propofol, bioavailability was 32±7%. Nasal bioavailability was greater than the reported oral bioavailability of DMP 755 in dogs, and was quite consistent. Because anesthesia affects nasal bioavailability, an effect that may depend on the absorption half-life of the test compound, a conscious or lightly sedated animal model is preferred.