Tissue cage experiments with beta-lactam antibiotics in rabbits

An animal model in which antibiotic concentrations can be meausred in intersittial fluid (IF) withdrawn from subcutaneous tissue cages has been used. Although the physiological significance of IF is not well established, this model allowed the comparison of 1) two pharmacological forms of the same drug (bacampicillin and ampicillin were compared after a single oral dose; and 2) drugs of the same group in a single i.m. injection study and in a cumulative effect study. These data provide new criteria for clinical choice of antibiotics. A rapid penetration into IF can be explained by a low degree of serum protein binding, but a highly bound drug is not restricted to the intravascular space. In this animal model we have also shown that an 0.25 h i.v. infusion of cephalothin induced higher IF levels than an i.v. bolus injection and an 1 h i.v. infusion. Using a single i.v. bolus injection of various cephalosporins, we have shown that a two open compartment model cannot explain both serum and IF data. Sustained late IF levels suggested the hypothesis of a deep compartment.