This study determined the pharmacokinetic disposition of cefonicid. A single dose of 7.5 mg/kg of body weight was administered to five healthy volunteers as a 5-min intravenous infusion. Multiple plasma and urine samples were collected for 48 h. Peak plasma concentrations ranged from 95 to 156 ,ug/ml and fell slowly (mean plasma half-life, 4.4 + 0.8 h), so that levels after 12 h were in the range of 6 to 12 ,ug/ml. Urinary concentrations were high but variable and ranged from 100 to 1,000 ,ug/ml for the first 12 h after the dose and averaged 84 ,ug/ml between 12 and 24 h. Plasma and renal clearances were 0.32 ± 0.06 and 0.29 ± 0.05 ml/min per kg, respectively. An average of 88 ± 6% of the dose was excreted unchanged in the urine over 48 h. The mean steady-state volume of distribution was found to be 0.11 ± 0.01 liters/kg.More than 90% of strains of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, indole-positive Proteus spp., and Enterobacter spp. are inhibited by 12.5 ,ug or less of cefonicid per ml (1,6). This range of activity is at least partly explained by the relative resistance of cefonicid to hydrolysis by various beta-lactamases elicited by gram-negative organisms (6). Most strains of Serratia marcescens are resistant, as are all strains of Pseudomonas aeruginosa (4). Cefonicid is less active than cefamandole or the older cephalosporins against gram-positive cocci. However, nearly all strains of Staphylococcus aureus are inhibited by -6.25 ,ug/ml. In animal experiments, cefonicid appears to have a longer elimination half-life as compared with cefamandole or cefazolin (1). This was recently confirmed in humans (7), in whom a half-life of approximately 3.5 h was noted after intravenous or intramuscular administration. This feature and the in vitro activity of the compound make cefonicid a potentially very useful antibacterial agent. Thus, the purpose of this study was to determine the pharmacokinetic disposition of cefonicid after a single intravenous dose in healthy volunteers.MATERIALS AND METHODS Experimental procedure. Five healthy adult male volunteers participated in the study. Informed consent was obtained from each subject, and the guidelines for human experimentation of the U.S. Department of Health and Human Services and of our institution were followed in the conduct of this clinical research.A panel of laboratory tests consisting of a complete blood count, measurement of the concentration of sodium, potassium, chloride, bicarbonate, calcium, phosphate, and creatinine in serum and urea N in blood, liver function tests, urinalysis, creatinine clearance, direct Coombs test, and a complete medical history and physical examination were carried out before and after drug administration. The subjects ranged in age from 26 to 34 years and in weight from 79 to 88 kg. Creatinine clearance in the subjects averaged (± standard deviation) 117.2 ± 8.5 ml/min. Cefonicid (1,000-mg vials) was reconstituted with 2.5 ml of sterile water for injection, so that each milliliter of solution contained 330 m...
