Pharmacokinetics of cephalosporins in normal and septicemic rabbits

Abstract

The differences in the pharmacokinetics of cefotaxime, moxalactam, and CPW 86-363, a new expanded-spectrum cephalosporin, were studied in healthy rabbits and in rabbits infected intravenously with Streptococcus pneumoniae. The pharmacokinetic analysis of concentration-time courses in the sera of infected animals according to a two compartment-model evidenced a clear decrease of drug fractions in the central compartment but enhanced drug fractions in the peripheral compartment. The shift was more pronounced in animals which received CPW 86-363 (60%; P less than 0.05) than in those which received cefotaxime (20%) or moxalactam (5%). Corresponding increases in drug concentration were observed in soft tissue interstitial fluid; therefore, the areas under the curve and mean residence times in the soft tissue interstitial fluid of infected rabbits were prolonged. The shift of drug fractions from the central compartment to other body fluid compartments during infection was thought to be due to cardiovascular changes associated with fever. No changes in serum binding of the three drugs were found during the course of the infection. The quantitative differences in the extent of altered distribution properties of the drugs might be due to variations in the physicochemical properties of the drugs.