MIGRATING MOTOR COMPLEX OF THE INTESTINE AND ABSORPTION OF A BILIARY EXCRETED DRUG IN THE DOG

The role of the migrating motor complex (MMC) of the small intestine i n the absorption of an enterally administered marker (tolfenamic acid, TA) used to investigate enterohepatic recycling was studied in the fa sted dog. TA was rapidly and extensively absorbed in the duodenum as w ell as in the ileum. In contrast, the conjugated form of TA (CTA) was not absorbed in the duodenum but only in the ileum, i.e., after bacter ial hydrolysis. By administering CTA in the duodenum at different phas es (I and II) of the MMC, it was shown that CTA had to be propelled fr om the duodenum to the ileum by the motor activity of the MMC. Under t hese conditions, the peak plasma TA concentration was only observed wh en phase II of the MMC present in the duodenum at the time of CTA admi nistration arrived in the ileum. The estimated mean transit time of CT A from the duodenum to ileum was 45 min and the mean hydrolysis time o f CTA to TA was about 75 min. It was concluded that 1) in the fasted d og, a relatively long delay must exist between bile excretion of a con jugate and the reabsorption of its free moiety in the ileum and 2) a r ealistic physiological model of enterohepatic recycling must take into account the MMC pattern of the intestine when drugs are administered to animals in the fasted state.