Metabolism of dibucaine. II. Disposition and metabolism of dibucaine in rats.

Abstract

The disposition and metabolism of dibucaine were studied in rats. After intraperitoneal administration of 3H-labelled dibucaine, the blood concentration of total radioactivity reached a maximum at 10 min and declined thereafter, with a biphasic curve having half-lives of 37.7 min and 11.2 h. Radioactivity in the tissues after administration was high in small intestine, lung, spleen, liver, kidney and stomach. Urinary and fecal excretion of radioactivity were 39.4 and 49.0% of the dose, respectively, in 3 d after administration. Biliary excretion of radioactivity in bile duct-cannulated rats was 53% of the dose within 48 h. About 40% of urinary, fecal and biliary excretion was found in the basic metabolites, and about 12% of urinary excretion was in the acidic metabolites. In addition, 9.5% of urinary excretion and 39.5% of biliary excretion were conjugated metabolites which could be extracted following enzymatic hydrolysis. Most of the conjugates were glucuronides. Remaining metabolites were highly polar and water-soluble ones which were not hydrolyzed by enzyme treatment and could not be extracted into organic solvents.