Influence of endotoxin on the distribution of cephalosporins in rabbits

The concentration: time courses of six different cephalosporins were studied in serum and interstitial fluid from issue cages after intravenous injection in normal and endotoxaemic rabbits. Circulatory and metabolic changes induced by endotoxin were similar to the altered organ function observed in patients with septicaemia. A significant shift of drug fractions, increase in the volume of distribution and prolonged mean residence times were observed in this model with ceftazidime, ceftriaxone and CPW 86-363, and were the result of specific changes in the peripheral compartment. The opposite findings were observed with cefotaxime, while latamoxef and cefoperazone resulted in no changes.