Metabolic fate of SCE-129, a new antipseudomonal cephalosporin, after parenteral administration in rats and dogs.

Abstract

Disposition of [(14)C]SCE-129 was studied in rats and dogs after intramuscular (i.m.) or intravenous (i.v.) injection. In rats, the plasma level of i.m. [(14)C]SCE-129 attained a peak at 15 min after dosing and then declined with a half-life of 35 min, whereas the half-life after an i.v. dose was 26 min. The area under the plasma level curve within 2 h after the i.m. dose was 85% of that after the i.v. dose. Intramuscular injection of [(14)C]SCE-129 into dogs gave a peak plasma level at 30 min and a half-life of 60 min. In both rats and dogs, the plasma levels of (14)C were closely similar to those of the unchanged antibiotic, which was weakly bound to plasma protein. The rat tissue level of i.m. [(14)C]SCE-129 was maximum at 15 min, with the highest concentration in the kidney, followed by plasma, adrenal, lung, heart, thymus, gastrointestinal wall, and liver, and the lowest in the brain. The antibiotic barely entered erythrocytes of rats and dogs. Whole-body autora-diographic studies showed that i.m. [(14)C]SCE-129 scarcely crossed the rat placenta. (14)C was detected in the milk of rats given i.m. [(14)C]SCE-129. In both rats and dogs, almost all of the dosed (14)C was excreted in urine within 24 h as the unaltered antibiotic, with only small amounts appearing in feces via bile. Thus, these findings evidenced a rapid absorption and wide distribution of i.m. SCE-129, followed by extensive renal elimination as the unaltered antibiotic.