INTRANASAL ABSORPTION OF THE PLATELET GLYCOPROTEIN IIB IIIA RECEPTOR ANTAGONIST, DMP-755, AND THE EFFECT OF ANESTHESIA ON NASAL BIOAVAILABILITY/

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 dete rmined by measuring plasma concentrations relative to those after intr avenous dosing. DMP 755 is an ester prodrug, and bioavailability refle cts concentrations of the acid hydrolysis product. Nasal bioavailabili ty in dogs anesthetized with pentobarbital was 85 +/- 4%, whereas in d ogs anesthetized with the short-acting anesthetic propofol, bioavailab ility was 32 +/- 7%. Nasal bioavailability was greater than the report ed oral bioavailability of DMP 755 in dogs, and was quite consistent. Because anesthesia affects nasal bioavailability, an effect that may d epend on the absorption half-life of the test compound, a conscious or lightly sedated animal model is preferred.