METABOLIC FATE OF SCE-963, A NEW BROAD-SPECTRUM CEPHALOSPORIN, AFTER PARENTERAL ADMINISTRATION IN RATS AND DOGS

Abstract

Intramuscularly injected ¹⁴C-SCE-963 was absorbed by rats to give a maximum plasma level at 10-15 minutes after dosing and an apparent half-life of 25 minutes. In this species, the plasma half-life after intravenous injection was 27 minutes. Intramuscular injection of the labeled antibiotic to dogs gave a peak plasma level at 30 minutes, followed by decay with a half-life of 53 minutes. In both rats and dogs, the plasma levels of radioactivity were essentially the same as those of the unchanged antibiotic, which was moderately bound to plasma protein. ¹⁴C-SCE-963 was hardly taken up by the erythrocytes of these animals. After intramuscular administration of ¹⁴C-SCE-963 to rats, the tissue level of radioactivity was maximum at 15 minutes with the highest concentration in the kidney, followed by liver, plasma, intestine and lung, and the lowest in brain. Whole-body autoradiography of pregnant rats showed that ¹⁴C-SCE-963 scarcely crossed the placenta. In both rats and dogs, larger amounts of the dosed radioactivity was excreted in urine as the unchanged antibiotic, the remainder appearing in feces via bile. This finding indicated that the metabolism of SCE-963 was only a minor process in the elimination of the antibiotic. ¹⁴C-SCE-963 was almost completely eliminated from the body of both animals within 24-48 hours. Radioactivity was detected in the milk of rats given ¹⁴C-SCE-963 intramuscularly.