Animal pharmacokinetics and toxicology of cefotetan--a new cephamycin antibiotic

In animal pharmacokinetic studies the biological half-lives of cefotetan were 13.0 min in mice, 15.9 min in rats, 30.5 min in rabbits, 55.5 min in dogs and 77.9 min in rhesus monkeys. The acute intravenous LD50 values (g/kg) were 6.4 and 5.0 in male and female mice, respectively, and 8.5 and 6.8 in male and female rats, respectively. Six-month repeated dose studies of 30 to 1000 mg/kg per day intraperitoneally in rats and 100 to 600 mg/kg per day intravenously in rhesus monkeys showed no notable organ toxicity. A teratogenicity study in rats indicated that cefotetan had no adverse effects on fetal and postnatal development. The nephrotoxicity of cefotetan in rabbits was considerably less than that of cefazolin.