Alterations of pharmacokinetic properties of gentamicin, penicillin G and two cephalosporins in septicaemic rabbits

The pharmacokinetics of gentamicin, penicillin G, latamoxef and CPW 86-363, a novel third generation cephalosporin, were studied in healthy and septicaemic rabbits. Elevation of body temperature in infected animals was paralleled by statistically significant decreases in serum drug levels during the early stages of the distribution phase for penicillin G, latamoxef and CPW 86-363 whereas gentamicin showed increased serum drug levels during the early period. No significant differences were seen in tissue fluid levels (STIF) or normal and septicaemic rabbits for the four antibiotics used. Haemodynamic alterations and an increased permeability of blood vessel walls are presumed to contribute to changes in distribution properties of various drugs during experimental septicaemia. The qualitative differences among the antibiotics tested seem to be related to their physico-chemical characteristics.