REGIONAL DRUG-DELIVERY .1. PERMEABILITY CHARACTERISTICS OF THE RAT 6-DAY-OLD AIR POUCH MODEL OF INFLAMMATION

Purpose. To determine the permeability characteristics of the rat air pouch model of inflammation using permeability extremes within which t he NSAIDs S[+] ibuprofen, piroxicam and diclofenac could be evaluated. Methods. Permeability was calculated using concentration data obtaine d following intrapouch and intravenous administration of [H-3]-water, [C-14]-urea, [C-14]-inulin and [I-125]-albumin and compared to similar data obtained for the three NSAIDs. Results. Similar permeability val ues (5-6.5 ml hr(-1)) were obtained for the three NSAIDS which fell be tween the permeability extremes of the molecular weight markers [H-3]- water (9.7 ml hr(-1)), [C-14]-urea (6.8 ml hr(-1)), [C-14]-inulin (1.0 ml hr(-1)) and [I-125]-albumin (0.6 ml hr(-1)). Coadministration of e quipotent anti-inflammatory doses of the NSAIDs did not affect local b lood flow to the air pouch (as assessed by urea kinetics) but did redu ced vascular permeability (as assessed by albumin flux into the pouch) . Conclusions. Comparison of the NSAIDs with the permeabilities of the molecular weight markers indicates that a perfusion rate limitation p robably exists. Systemic absorption is complete over the first two hou rs following intrapouch administration of the NSAIDs, therefore albumi n flux into the pouch is insufficient to materially affect the permeab ility of the NSAIDs. However, subsequently (post 5hr) albumin concentr ation in the pouch rises sufficiently to lower the effective flux of t he NSAIDS.