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, gut tissue, and blood in anesthetized rats.
Methods: Sodium salicylate (5.4 mg as SA) in 0.4 ml normal saline was administered into a closed 10-cm jejunal loop. Drained mesenteric blood from the loop area was collected every minute, while lost blood was replaced through infusion of oxygenated blood from donor rats. At 3, 10, 20, 40, or 60 min after dosing, SA remaining in lumen, accumulating in gut tissue, and appearing in blood were analyzed by HPLC. All the data were fitted into a linear two-consecutive (lumen and gut tissue) first-order kinetic model.
Results: 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 absorption time from the lumen and mean transit time in gut tissue of SA were 20.4 and 18.5 min, respectively.
Conclusions: The above results indicate that gut tissue may act as a reservoir for drug accumulation during the first pass after oral absorption. Thus, the rate of transport of drug into blood circulation after oral administration may significantly differ from the true rate of absorption through the gut membrane. The potential transport resistance from gut tissue to blood should probably be considered in the modeling of GI absorption.