Pharmacokinetics of cefotetan (YM09330) in humans

The pharmacokinetics and safety of cefotetan (YM09330) were examined after intravenous administration of single and multiple doses to normal volunteers. Cefotetan was well tolerated in single doses of 500 to 3,000 mg and in multiple doses of 500 and 1,000 mg at 12-h intervals for 1 and 3 days. These doses produced high plasma levels. The half-life (3 h) of cefotetan was longer than that of cefazolin. There was no evidence of drug accumulation in the plasma in the multiple-dose study. Mean recoveries of cefotetan in urine within a 24-h period were 74.5 to 88.4% of the dose, regardless of the route of administration and the dosage. The tautomer of cefotetan accounted for approximately 5% of the dose excreted in the urine. No tautomer was detected in plasma. Concentrations of drug in plasma and urine measured by microbiological assay were in good agreement with those measured by high-pressure liquid chromatography.