Abstract

The metabolism of C¹⁴-labeled chlortetracycline following oral, intraperitoneal and intravenous administration in the rat and intravenous administration in the dog has been studied. In addition a comparison of the routes of excretion of total radioactivity from C¹⁴-chlortetracycline, C¹⁴-4-epichlortetracycline, H3-tetracycline and C¹⁴-demethylchlortetracycline after intravenous administration to these animals was undertaken.

The recovery of the administered radioactivity in the urine and feces of rats dosed orally or intravenously with C¹⁴-chlortetracycline varied from 76% to 97% of the dose after 48 to 72 hours. At this time only 33% to 70% of the administered microbiological activity was found. That portion of the dose excreted in the urine of dogs given this compound intravenously showed a similar relationship with the recovery of radioactivity being 48% while the microbiological recovery was 13%. The excreted C¹⁴, when examined by paper strip chromatography, was associated with two major components. These corresponded in R_f to unchanged chlortetracycline and to the microbiologically inactive 4-epichlortetracycline. Treatment of these components with acid or base yielded degradation products which were chromatographically similar to the respective anhydro or iso derivative. In the excreta of some of the animals, small amounts of a blue fluorescing material that corresponded to isochlortetracycline were observed.

Following intravenous administration of C¹⁴-labeled chlortetracycline, 4-epichlortetracycline or demethylchlortetracycline or H³-labeled tetracycline, significant amounts of radioactivity were excreted via the feces. Chlortetracycline and 4-epichlortetracycline were excreted to the greatest extent (40 to 50% of the dose) by this pathway followed in order by demethylchlortetracycline (15 to 30%) and tetracycline (9 to 20%).