Abstract

In this paper a method is introduced to study both intestinal and liver metabolism in the intact rat by cannulation of the jugular vein, carotid artery, pyloric vein (into the portal vein), and bladder. In this preparation, the rat received an initial dose followed by iv (I) and then intraportal (II) infusions. Gentisamide (2,5-dihydroxybenzamide, GAM) was used since it forms monosulfate (GAM-2S and GAM-5S) and monoglucuronide (GAM-5G) conjugates, metabolites that are not further metabolized. After administration of tracer amounts of radiolabeled gentisamide ([3H]GAM), the concentration ratio of [3H]GAM in the portal vein and carotid artery [CPV(I)/CA(I)] during iv infusion, and the ratio of carotid artery concentrations for intraportal to iv infusions [CA(II)/CA(I)] provided the intestine and liver availabilities, respectively; the corresponding extraction ratios for the intestine and liver were 0.26 to 0.27 and 0.37 to 0.41. Similar concentration ratios for the conjugates during iv administration [CPV(I)/CA(I)] showed intestine formation of GAM-5G, and to a lesser extent, GAM-2S, since the ratios exceeded unity; GAM-5S was not formed by the intestine since the ratio was unchanged. The ratio of the carotid arterial concentrations for intraportal to iv infusions that revealed hepatic formation showed similar values (1.77 and 1.71) for GAM-2S and GAM-5S, but variable (decreases and increases) GAM-5G values, whose mean value approximated unity. All findings were consistent with data obtained from the perfused rat liver preparation and the combined perfusion of rat intestine-liver preparation, where GAM-5G and GAM-2S were shown to be formed by the intestine, and where sulfation was the preferred pathway in the liver.(ABSTRACT TRUNCATED AT 250 WORDS)