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Fifteen patients less than 2 months old with bacterial infections caused by pathogens known or presumed to be sensitive to cefoxitin were studied. Cefoxitin was administered as an i.v. bolus injection over 15 min, every 8 h for 6 to 12 days, to a total daily dosage of 90 mg/kg. In 14 patients cefoxitin therapy resulted in eradication of the pathogen and in recovery from clinical signs of infection. Only one patient did not respond to cefoxitin therapy. No adverse clinical or haematological effects definitely caused by cefoxitin were observed. Plasma and urine samples collected after the first dose were assayed for cefoxitin by HPLC. Pharmacokinetic data indicated larger apparent volume of distribution (0.5 1/kg), a smaller plasma clearance (0.27 1/h/kg) and a longer half-life (1.43 h) than in adults. The plasma half-life was inversely correlated (p less than 0.05) to the postnatal age of the patients. Cefoxitin may be safely used in infants with infections caused by susceptible pathogens.

The pharmacokinetics of cefoxitin was studied in patients with renal impairment during haemofiltration and in the intervening periods after administration of 30 and 15 mg/kg of the drug, respectively. Different pharmacokinetic patterns were established during haemofiltration and in the interim period, with average elimination half-lives of 11.85 +/- 4.3 and 3.41 +/- 0.6 h, respectively. The average fraction of the cefoxitin dose eliminated in haemofiltration was 0.62 +/- 0.11, more than that established in haemodialysis. In patients with terminal renal impairment undergoing haemofiltration every 48 h, a dose of 15 or 30 mg/kg is recommended at the start and at the end of each haemofiltration session.

Intravenous doses of 0.5, 1, and 2 g cephalothin and cefoxitin, a semi-synthetic cephamycin antibiotic highly resistant to bacterial cephalosporinase, were infused over a period of 3 minutes into 18 normal adult males by a randomized, crossover design. Serum and urine data on cefoxitin best fit a two-compartment open model. Serum concentrations following cefoxitin were higher and more prolonged and urine recoveries higher than those following equal doses of cephalothin. The terminal serum half-life of cefoxitin was longer at all dose levels. Renal clearance of cephalothin-like activity exceeded that of cefoxitin, which may possess dose-dependent kinetics. Whereas cephalothin has been reported to metabolize by greater than 35% to the less active desacetyl form, cefoxitin was metabolized by 0.1 to 6% to the descarbamyl form in individual subjects.

The pharmacokinetics of cefoxitin was studied in 6 healthy volunteers and in 5 patients with a pleural effusion after administration of a single dose of 30 mg/kg i.v. infusion. The serum and pleural fluid concentrations of cefoxitin were determined microbiologically. The elimination half-life of the antibiotic from pleural fluid in all cases was 2-3 fold longer than from serum, which shows a difference between the kinetic elimination processes of the antibiotic from the two fluids. The slow elimination of cefoxitin from pleural fluid facilitates its accumulation in this compartment during a multiple dosage regimen.

The use of lidocaine HCL solution at concentrations of 0.5 and 1.0% to reconstitute sodium cefoxitin relieves the pain associated with intramuscular injections of the antibiotic. Cefoxitin absorption by the intramuscular route is initially rapid and is virtually complete. Peak serum concentrations, corresponding to about one-half those of a comparable intravenous infusion, are achieved in 30 min. Continuing absorption tends to maintain higher serum concentrations for longer times. Renal clearance and serum half-life of cefoxitin do not appear to be affected by lidocaine at its effective anaesthetic concentrations.

The pharmacokinetics of cefoxitin was examined in 9 patients undergoing peritoneal dialysis for chronic renal failure. Cefoxitin was administered intraperitoneally in the dialysate fluid every 6 h for 24 h, in two different concentrations, 50 micrograms/ml and 100 micrograms/ml. The plasma half-life of cefoxitin was 20.2 h. The major route of elimination was non-renal, with a clearance of 8.0 ml/min. Peritoneal clearance was 4.1 ml/min. As expected, renal clearance was negligible. The peak plasma concentrations of cefoxitin at the two dose levels used were 7 micrograms/ml and 15 micrograms/ml, respectively, when assayed by HPLC, and 12 micrograms/ml and 24 micrograms/ml when determined by a microbiological assay. The cefoxitin concentration in the dialysate decreased from 50 micrograms/ml to 14 micrograms/ml and from 100 micrograms/ml to 37 micrograms/ml during the 6 h of its retention in the peritoneal cavity.

The pharmacokinetics of Cefoxitin was studied in 8 cirrhotic patients with ascites after i.v. administration of a single 30 mg/kg dose. Concentrations of cefoxitin in serum and in ascitic fluid were determined simultaneously and by a microbiologic plate diffusion method. The antibiotic followed a two-compartment open kinetic model. In ascitic fluid, Cefoxitin reached its maximum concentration of 32.80 +/- 13,78 micrograms/ml 2 h after administration. The mean elimination constant from ascitic fluid was 0.201 +/- 0.008 h(-1), significantly lower (p less than 0.05) than the slow disposition phase constant (beta = 0.556 +/- 0.17 h(-1)). At the dose studied and with a dosage interval of 8 h, the level of antibiotic in the ascitic fluid would be maintained at a value greater than the MIC of most cefoxitin-sensitive organisms.

The pharmacokinetics of cefoxitin have been determined after a single i.v. injection of 15 mg/kg body weight in 10 patients with normal renal function and 20 patients with varying degrees of renal impairment. The kinetics of the antibiotic followed an open two-compartment model. In patients with normal renal function the following pharmacokinetic parameters were found: alpha = 8.66 h-1 beta = 1.21 h-1 K12 = 3.47 h-1 K21 = 3.17 h-1 K13 = 3.15 h-1 Vc = 4.24 l. Vp = 4.87 l. Vdss = 9.11 l. In the patients with renal impairment there was a significant decrease in alpha, beta, K12, K21 and K13, and an increase in the apparent volume of distribution. The degree of plasma protein binding in patients with normal renal function was 73.6% and this was diminished in patients with renal impairment. A linear relationship between K13 of cefoxitin and creatinine clearance was demonstrated. The dosage regimen for patients with renal impairment should be adjusted by modifying the dosage interval whilst maintaining the amount administered.