USE OF EVERTED INTESTINAL RINGS FOR IN-VITRO EXAMINATION OF ORAL ABSORPTION POTENTIAL

The ability to predict in vivo oral absorption potential based on ex v ivo screening in an everted intestinal ring model was examined. In vit ro drug accumulation in cross sectional rings of everted rat jejunum w as determined with 12 compounds whose in vivo absorptions (as distinct from bioavailabilities) are well characterized. The compounds examine d 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 deter mined. Light microscopic observation indicated that the mucosal tissue remained intact up to 3 h after the intestine was excised. Accumulati ons of two nonabsorbable markers were also determined as measures of t issue integrity. A strong correlation (slope = 23 pmol/mg of tissue we ight per percent oral absorption, P = 0.9430 by linear regression anal ysis) of in vitro uptake into everted rings from a 10 mM drug solution versus the known in vivo bioavailability for each compound was observ ed. These results indicated that under appropriate conditions, in vitr o uptake of drug by the everted intestinal ring model closely parallel ed known in vivo bioavailability and was relatively independent of pH, cosolvent, and tissue origin.