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Rats and dogs were given a single 20-mg/kg dose of [14C]carumonam intramuscularly or intravenously. In rats, the level in plasma of [14C]carumonam administered intramuscularly peaked (29.1 micrograms/ml) 15 min after dosing and then declined with an apparent elimination half-life of 16.2 min. Intramuscular injection of [14C]carumonam to dogs gave a peak level (36.8 micrograms/ml) in plasma at 20 min and an apparent elimination half-life of 51.7 min. After administration of the intravenous dose, apparent elimination half-lives were 13.1 and 52.7 min in rats and dogs, respectively. In both animals, the radioactivity in plasma was made up largely (greater than 80%) of unchanged carumonam, which was protein bound to only a small extent. In rats given [14C]carumonam intramuscularly, radioactivity was distributed widely in tissues, with relatively high concentrations in the kidney and liver. The radioactivity concentration in the rat fetus was relatively low, as was that in milk. In both rats and dogs carumonam did not undergo extensive metabolism; the most prominent metabolite was AMA-1294, the compound resulting from beta-lactam ring hydrolysis. [14C]carumonam and metabolites were mostly eliminated from the bodies within 72 h in rats and 120 h in dogs. In both animals, a large amount of the dosed radioactivity was excreted in the urine largely as unchanged antibiotic. The remainder was eliminated in the feces via bile. AMA-1294 was eliminated from the bodies of rats and dogs at a considerably slower rate than was unchanged carumonam. In rats, [14C]carumonam was eliminated by both glomerular filtration (67%) and tubular secretion (33%); the renal elimination of [14C]AMA-1294 was only by glomerular filtration.

Disposition of carumonam (AMA-1080/Ro 17-2301), a new N-sulfonated monocyclic beta-lactam, in rats and dogs