Human Pharmacokinetics of a New Broad-Spectrum Parenteral Cephalosporin Antibiotic, Ceforanide

Abstract

The pharmacokinetics of the l-lysine salt of ceforanide were studied after intravenous administration of 1132 and 2264mg as 30-min constant-rate infusions and after intramuscular administration of 556 and 1132mg. The peak intravenous plasma concentrations were 136 and 222 μg/ml at termination of infusion, and 12-hr trough concentrations were 5.9 and 9.0 μg/ml, respectively. The peak intramuscular plasma concentrations were 38 and 74 μg/ml at 1.0–1.3hr after dosing, and 12-hr trough concentrations were 3.9 and 6.7 μg/ml, respectively. When 19 successive intravenous and intramuscular doses at these levels were administered at 12-hr intervals, there was no tendency toward drug accumulation. The major drug elimination route was urinary excretion; 85% of the dose was excreted unchanged in the urine within 12 hr, and no metabolites with antibiotic activity were observed in urine. The mean terminal plasma half-life was 2.98 hr, the mean plasma protein binding was 80.6%, the steady-state volume of distribution was 12 liters, the plasma clearance was 45.9 ml/min/1.73m2, and the renal clearance was 34.9 ml/min/1.73m2. The pharmacokinetic properties and antibacterial activity spectrum indicate that this antibiotic should be effective in treating human bacterial infections when administered at 12-hr intervals. It is presently under clinical investigation.