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 g iven over 30 min in a cross-over-designed study, to each of six health y 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, du ring which the blisters healed, the study was repeated at the other do se level. Following the 1-g dose, the mean peak concentration in plasm a was 83.8 mu g/ml, and after the 2-g dose it was 142.6 mu g/ml. The m ean peak concentrations in the inflammatory fluid were 37.9 and 63.3 m u g/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 concentr ation-time curves) were 109.9 and 110.5% following doses of 1 and 2 g, respectively. The proportions of the administered drug recovered in t he urine by 24 h were 87.6 and 85.7%, respectively. Our results indica te that FK-037 should prove to be efficacious in the treatment of a wi de range of systemic infections.