INTRANASAL ABSORPTION OF DIFFERENT AQUEOUS FORMULATIONS OF ANGIOPEPTIN - IN-VIVO BIOAVAILABILITY STUDY

The bioavailability of angiopeptin in rabbits after intranasal adminis tration of three aqueous formulations has been studied. In each case a total amount of 750 mu g angiopeptin was administered. A simple aqueo us solution and an aqueous solution supplemented with 5% glycofurol 75 (GF) resulted in bioavailabilities of 133%, whereas the bioavailabili ty of angiopeptin was 53%, when 1% sodium glycocholate (GC) was added to the aqueous solution. The observed reduction in bioavailability fro m this formulation may be due to precipitation of angiopeptin in the n asal mucus layer, as the formulation containing GC tended to precipita te. The main indication of angiopeptin is inhibition of restenose of c ononary arteries after angioplasty or heart transplantation. The pharm acokinetics of angiopeptin could be described by a two-compartment mod el, and the plasma half-life was about 1.5 h. Addition of GF and GC re sulted in faster absorption, the t(max) being 16 and 14 min, respectiv ely, as compared with 31 min for the simple aqueous solution. The fast er absorption with GF and GC is not considered of therapeutic importan ce, but rapid absorption may give rise to more reproducible dosing in the clinical situation. C-max was about 2.8 ng/ml for all three formul ations.