Abstract

Segments of rat small intestine, split longitudinally or formed into everted sacs and suspended in an oxygenated solution of phenacetin in modified Krebs-Ringer-bicarbonate buffer, metabolize phenacetin to N-acetyl-p-aminophenol. The oral administration of 3,4-benzpyrene to rats increases the O-dealkylation of phenacetin by subsequently prepared everted intestinal sacs and results in an increase in the amount of N-acetyl-p-aminophenol and a decrease in the amount of phenacetin transferred to the serosal side of the sacs. These data indicating that changes in intestinal metabolism of phenacetin can influence the amount of phenacetin that is transferred unchanged from the mucosal to the serosal side of the small intestine suggest that intestinal metabolism may play a role in determining the bioavailability of orally administered phenacetin. The preparation employing longitudinally split segments of intestine provides a very simple, sensitive technique for studying the in vitro intestinal metabolism of phenacetin and possibly other drugs in the rat.