Human pharmacokinetics of a new braod-spectrum parenteral cephalosporin antibiotic, ceforanide.
The pharmacokinetics of the l-lysine salt of ceforanide were studied after intravenous administration of 1132 and 2264 mg as 30-min constant-rate infusions and after intramuscular administration of 556 and 1132 mg. The peak intravenous plasma concentrations were 136 and 222 microgram/ml at termination of infusion, and 12-hr trough concentrations were 5.9 and 9.0 microgram/ml, respectively. The peak intramuscular plasma concentrations were 38 and 74 microgram/ml at 1.0-1.3 hr after dosing, and 12-hr trough concentrations were 3.9 and 6.7 microgram/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/1.73 m2, and the renal clearance was 34.9 ml/min/1.73 m2. 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.
D000328:Adult; D001798:Blood Proteins / Q000378:metabolism; D002435:Cefamandole / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000652:urine; D002511:Cephalosporins / Q000031:analogs & derivatives*; D006801:Humans; D007267:Injections; D007700:Kinetics; D008297:Male; D011485:Protein Binding; D013997:Time Factors
D001798:Blood Proteins; D002511:Cephalosporins; D002435:Cefamandole; C012653:ceforanide