The utility of diffusion chambers as models for the description of drug disposition

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Abstract
Tissue cages were employed to explore the diffusion processes of several cephalosporins into extravascular fluids. Concentrations of cefotaxime in serum and in subcutaneous chambers increased proportionally to the amount of the drug injected. Administration of single equal doses of cephalothin, cephaloridine and cefotaxime resulted in different concentration-time courses in the serum and in diffusion chambers. These observations suggest that diffusion chambers are linked to the tissue at the implantation site. None of the classical compartmental approaches can be applied to evaluate the kinetics of drug diffusion into tissue cages. Correlations of total or non-protein bound drug concentrations in tissue cages to those in the peripheral compartment assumed concentration and time dependent diffusion processes. No specific diffusion constant based on the law of Fick could be derived for the diffusion chambers used in this study. Concentration-time courses in serum and interstitial fluid can be simultaneously evaluated according to pharmacokinetic-pharmacodynamic models. Based on the equation describing the effect site this model can be used to simulate drug concentrations in tissue cages by varying the dose size or the dose interval.