Studies on the absorption, distribution and excretion of radioactivity after intravenous and intraperitoneal administration of 14C-methyl ester of amphotericin B.

Abstract

Distribution and balance studies with carbon-14-labeled amphotericin B methyl ester (AME) were carried out in mice. The radioactive AME was administered by either the intraperitoneal (i.p.) or intravenous (i.v.) route. In the organ distribution study, the percent radioactivity accumulating in the lung of i.v. treated mice at 1 hour after administration was about 150 times greater than that observed when the intraperitoneal route was used. No accumulation of radioactivity with time was detected in the kidneys of either the i.v. or i.p. treated mice. After 4 days, about 51% of the total radioactivity was excreted into the urine and feces of mice after i.v. administration, but only about 15% of the total radioactivity was excreted in the case of mice receiving radioactive AME by the i.p. route. In the identification of the substances excreted in the urine, thin-layer chromatography (TLC), radioactivity, and bioautographic evidence suggest that there was no detectable de-esterification of AME to the parent compound in mice treated either intraperitoneally or intravenously with AME.