Use of Everted Intestinal Rings for in Vitro Examination of Oral Absorption Potential

Abstract

The ability to predictin vivooral absorption potential based onex vivoscreening in an everted intestinal ring model was examined.In vitrodrug accumulation in cross sectional rings of everted rat jejunum was determined with 12 compounds whosein vivoabsorptions (as distinct from bioavailabilities) are well characterized. The compounds examined ranged from well‐ to poorly‐absorbed and included compounds absorbed by active and passive mechanisms. The effects of drug concentration, pH, cosolvents, and tissue origin site on drug accumulation were determined. Light microscopic observation indicated that the mucosal tissue remained intact up to 3 h after the intestine was excised. Accumulations of two nonabsorbable markers were also determined as measures of tissue integrity. A strong correlation (slope = 23 pmol/mg of tissue weight per percent oral absorption,r2= 0.9430 by linear regression analysis) ofin vitrouptake into everted rings from a 10 mM drug solution versus the knownin vivobioavailability for each compound was observed. These results indicated that under appropriate conditions,in vitrouptake of drug by the everted intestinal ring model closely paralleled knownin vivobioavailability and was relatively independent of pH, cosolvent, and tissue origin.