Phase I study of ceftizoxime, a new cephalosporin. Single-dose study

A phase I study of ceftizoxime, a new cephalosporin, was performed in 29 subjects. No abnormalities were observed in subjective symptoms, laboratory test results, or physical test results at estimated therapeutic doses of 500 mg intramuscularly, 500 and 1000 mg intravenously, and 2000 mg drip infusion. It is concluded, therefore, that the drug is safe for clinical use. The mean peak serum concentration was dose dependent. The mean serum concentrations of ceftizoxime in man at 5 minutes after 500 and 1000 mg by intravenous bolus were 58.4 and 112.8 micrograms/ml, respectively, which exceed the MIC80 against most pathogens tested. Thus, 500 or 1000 mg was estimated to be the therapeutic dose. The distribution volume of ceftizoxime was 16.0 to 18.6 liters, the total clearance was 135.6 to 154.9 ml/min, and the half-life in the beta-phase was 1.36 to 1.39 hours. Ceftizoxime is mainly excreted in the urine as unchanged drug, at an excretion rate in the 24-hour urine of approximately 80 per cent.