Pharmacokinetics and distribution in tissue of FK-037, a new parenteral cephalosporin.
A single 1-g or 2-g intravenous dose of the cephalosporin FK-037 was given over 30 min in a cross-over-designed study, to each of six healthy male volunteers, and the concentrations of the drug were measured in plasma and cantharides-induced blister fluid over the subsequent 12 h. Urine was collected over 24 h. After a washout period of 6 weeks, during which the blisters healed, the study was repeated at the other dose level. Following the 1-g dose, the mean peak concentration in plasma was 83.8 micrograms/ml, and after the 2-g dose it was 142.6 micrograms/ml. The mean peak concentrations in the inflammatory fluid were 37.9 and 63.3 micrograms/ml, respectively. The mean elimination half-lives from plasma and inflammatory fluid were 2.0 and 2.5 h, respectively, after 1 g and 2.0 h and 3.7 h, respectively, after 2 g. The amounts of penetration into inflammatory fluid (as assessed by ratios of areas under the concentration-time curves) were 109.9 and 110.5% following doses of 1 and 2 g, respectively. The proportions of the administered drug recovered in the urine by 24 h were 87.6 and 85.7%, respectively. Our results indicate that FK-037 should prove to be efficacious in the treatment of a wide range of systemic infections.
Wise
R
R
Department of Medical Microbiology, Dudley Road Hospital, Birmingham, United Kingdom.
Andrews
J M
JM
O'Neill
P
P
Jolley
A
A
Fowler
C
C
Rogge
M C
MC
D000328:Adult; D001768:Blister / Q000378:metabolism; D015296:Ceftizoxime / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D006801:Humans; D008297:Male; D014018:Tissue Distribution
C079769:cefoselis; D015296:Ceftizoxime