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The pharmacokinetics of YM09330, a new semisynthetic cephamycin, were determined after intravenous and intramuscular administration to experimental animals. Mean plasma levels of YM09330 at 30 min after intravenous administration of 20 mg/kg were 5.5 micrograms/ml for mice, 17 micrograms/ml for rats, 24 micrograms/ml for rabbits, 42 micrograms/ml for dogs, and 76 micrograms/ml for monkeys; plasma half-lives were 13.0, 15.9, 30.5, 55.5, and 75.6 min, respectively. The half-lives of YM09330 were longer than those of cefmetazole in all species tested. In monkeys, plasma levels of YM09330 were higher and more prolonged than those of cefazolin. In rats and dogs, the concentrations of YM09330 were highest in the kidneys, followed by the liver, plasma, lung, spleen, and heart in that order; they were similar to those of cefazolin in rats. Urinary excretion of YM09330 within 48 h of intravenous administrations was 67% of the dose in mice, 52% in rats, 74% in rabbits, 53% in dogs, and 60% in monkeys. In rats, 48% of the dose of YM09330 was detected in the plasma, urine, or bile. However, small amounts of an antibacterially active tautomer of YM09330 were recovered in the urine of mice, rats, and dogs, whereas large amounts of the tautomer were recovered in the urine of rabbits and monkeys. Serum protein binding of YM09330 was 30% of rats, 51% for rabbits, 39% for dogs, 87% for monkeys, and 91% for humans.

Pharmacokinetics of new broad-spectrum cephamycin, YM09330, parenterally administered to various experimental animals