title: Regional drug delivery I: permeability characteristics of the rat 6-day-old air pouch model of inflammation.
abstract: OBJECTIVE
  To determine the permeability characteristics of the rat air pouch model of inflammation using permeability extremes within which the NSAIDs S[+] ibuprofen, piroxicam and diclofenac could be evaluated.
  
  
  METHODS
  Permeability was calculated using concentration data obtained following intrapouch and intravenous administration of [3H]-water, [14C]-urea, [14C]-inulin and [125I]-albumin and compared to similar data obtained for the three NSAIDs.
  
  
  RESULTS
  Similar permeability values (5-6.5 ml hr-1) were obtained for the three NSAIDS which fell between the permeability extremes of the molecular weight markers [3H]-water (9.7 ml hr-1), [14C]-urea (6.8 ml hr-1), [14C]-inulin (1.0 ml hr-1) and [125I]-albumin (0.6 ml hr-1). Coadministration of equipotent anti-inflammatory doses of the NSAIDs did not affect local blood flow to the air pouch (as assessed by urea kinetics) but did reduced 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 probably exists. Systemic absorption is complete over the first two hours following intrapouch administration of the NSAIDs, therefore albumin flux into the pouch is insufficient to materially affect the permeability of the NSAIDs. However, subsequently (post 5hr) albumin concentration in the pouch rises sufficiently to lower the effective flux of the NSAIDs.
authors.affiliation: Department of Pharmacy, University of Manchester, United Kingdom.
authors.forename: S W
authors.initials: SW
authors.lastname: Martin
authors.forename: A J
authors.initials: AJ
authors.lastname: Stevens
authors.forename: B S
authors.initials: BS
authors.lastname: Brennan
authors.forename: M L
authors.initials: ML
authors.lastname: Reis
authors.forename: L A
authors.initials: LA
authors.lastname: Gifford
authors.forename: M
authors.initials: M
authors.lastname: Rowland
authors.forename: J B
authors.initials: JB
authors.lastname: Houston
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism*; D016503:Drug Delivery Systems; D007052:Ibuprofen / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy; D008954:Models, Biological; D010539:Permeability; D010894:Piroxicam / Q000378:metabolism; D051381:Rats; D013997:Time Factors; D014508:Urea / Q000378:metabolism / Q000493:pharmacokinetics
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D010894:Piroxicam; D014508:Urea; D007052:Ibuprofen