Experimental determination of a drug targeting index for S(+)ibuprofen using the rat air pouch model of inflammation.

Abstract

We have used the rat air pouch model of inflammation and S(+)ibuprofen as an experimental model system to enable the quantitative assessment of the pharmacokinetic determinants of site specific drug delivery. S(+)ibuprofen (50 & 1mg/kg) was administered directly into six day old air pouches immediately following the injection of the irritant carrageenan. Serial exudate and plasma samples were collected and analysed for ibuprofen by HPLC. The procedure was repeated following administration of S(+)ibuprofen (20 & 5mg/kg) intravenously. The parameters describing events in the air pouch and plasma indicated linear kinetics over the doses employed. The dose normalised AUCs were then used to formulate a quantitative measure of benefit for S(+)ibuprofen delivered directly to the air pouch. A Drug Targeting Index (DTI) was calculated from the ratio of AUC in the air pouch and plasma following direct intrapouch administration divided by the same ratio following intravenous administration and gave a value of 130. This pharmacokinetic measure of benefit represents the maximum advantage afforded by the site specific delivery of S(+)ibuprofen as the whole of the administered dose is delivered directly to the site of action.