STUDIES ON LANKACIDIN-GROUP (T-2636) ANTIBIOTICS

VIII. METABOLISM OF LANKACIDIN C 14-PROPIONATE IN RATS AND MICE

Abstract

The metabolic fate of lankacidin C 14-propionate-¹⁴C was studied in rats and mice. In these animals, the antibiotic administered orally was absorbed slowly, distributed widely in tissues and metabolized to be excreted mainly in bile. The metabolites in bile were then excreted into feces together with the unabsorbed radioactivity. The elimination of the antibiotic from the body was completed within 72 hours in both species. In rats, 77 and 6.5% of the radioactivity was excreted in feces and urine, respectively. In mice, 88 and 5.5% was eliminated into feces and urine, respectively. No significant amount of radioactivity was excreted in the expiratory air of either animal. After oral administration, the blood level of radioactivity reached a peak after 2 hours in rats and after 15 minutes in mice. Of the tissues tested, relatively higher concentrations were noted in liver, kidney, lung and spleen in rats and mice. At any time after the administration to mice, the levels of antibiotic activity in the infected region of liver, kidney and abdominal ascites were much higher than the blood levels. The antimicrobial activities in these tissues were mainly derived from the metabolites, lankacidin C and lankacidinol. The biliary metabolites identified were lankacidin C, lankacidinol, lankacyclinol, lankacidinol 14-P and T-2636 H in rats, and lankacidin C, lankacidinol and lankacyclinol in mice. The results obtained are discussed in relation to therapeutic activities of these antibiotics.