FIRST-PASS ACCUMULATION OF SALICYLIC-ACID IN GUT TISSUE AFTER ABSORPTION IN ANESTHETIZED RAT

Purpose. The purpose of this paper is to report the study on the first -pass accumulation kinetics of salicylic acid (SA) in gut tissue after absorption by simultaneously analyzing drug contents in the lumen, gu t tissue, and blood in anesthetized rats. Methods. Sodium salicylate ( 5.4 mg as SA) in 0.4 mi normal saline was administered into a closed 1 0-cm jejunal loop. Drained mesenteric blood from the loop area was col lected every minute, while lost blood was replaced through infusion of oxygenated blood from donor rats. At 3, 10, 20, 40, or 60 min after d osing, SA remaining in lumen, accumulating in gut tissue, and appearin g in blood were analyzed by HPLC. All the data were fitted into a line ar two-consecutive (lumen and gut tissue) first-order kinetic model. R esults, After absorption, significant amounts of SA accumulated in gut tissue before appearing in blood, e.g., at 3 or 20 min after dosing, 74.4 or 54.4% of absorbed SA accumulated in gut tissue, respectively. Practically all administered SA was recovered. The estimated mean abso rption time from the lumen and mean transit time in gut tissue of SA w ere 20.4 and 18.5 min, respectively. Conclusions. The above results in dicate that gut tissue may act as a reservoir for drug accumulation du ring the first pass after oral absorption. Thus, the rate of transport of drug into blood circulation after oral administration may signific antly differ from the true rate of absorption through the gut membrane . The potential transport resistance from gut tissue to blood should p robably be considered in the modeling of GI absorption.