Abstract
Ceftazidime (CAZ, SN401), a new parenteral cephalosporin antibiotic, was administered to 14 healthy male volunteers to study its tolerance and pharmacokinetics, by intramuscular injection (0.5g), 1-hour intravenous drip infusion (1g and 2g, in a cross over method), 2-hours intravenous drip infusion (2g), intravenous bolus injection (0.5g and 1g, in a cross over method) and multiple intravenous bolus injection (1g, at 12 hour intervals, 9 times).
1. In the examinations on tolerance such as subjective and objective symptoms, physical examinations, haematology, serum biochemistry, urinalysis, etc., no abnormalities attributable to CAZ were noted.
2. CAZ achieved high plasma levels after intramusclar and intravenous injections, corresponding to the increase of the administered dose. The plasma half life of CAZ was 1.6-2.1 hours, which was comparatively long, and even at 8 hours after administration, 0.9-5.7μg/ml of CAZ was detected in plasma.
3. CAZ was not inactivated in the body and about 90% of the dose was excreted within 12 hours after administration regardless of dose levels or administration routes.
4. In multiple dose of CAZ (1g of i. v. bolus injection, 9 times, 12 hourly), there was no variation in the plasma level and urinary excretion level, nor tendency to accumulation.
From the above results, CAZ was considered to be a safe drug with favorable pharmacokinetics, and from its high antibacterial activity, CAZ was expected to be a clinically effective drug in various infections.
