DISTRIBUTION PROPERTIES OF CEPHALOSPORIN IN MAN - PHARMACOKINETIC AND EXPERIMENTAL APPROACHES

  • 1 May 1987
    • journal article
    • research article
    • Vol. 25  (5) , 262-278
Abstract
The distribution properties of cephalosporin derivatives in man were analysed according to a two-compartment model and several pharmacokinetic approaches were followed to calculate disposition parameters. These calculations resulted in different parameters with the dimension of either volume or time or in relative values. These correlate significantly with experimentally derived disposition data, e.g., the volume of distribution of the peripheral compartment vs. the ratio of intravascular and extravascular AUC-values or the mean residence time vs. absolute drug levels at various extravascular sampling sites. Based on calculated disposition parameters, the various cephalosporin derivatives can be assigned to 4 different clusters with specific distribution properties, which correlate significantly with the daily dose recommended for the treatment of moderate to severe infections. This demonstrates the clinical relevance of mathematically derived distribution parameters for the prediction of drug levels in extravascular sites and for the design of therapeutically effective dose regimens. The usefulness of other pharmacokinetic concepts is discussed together with the graphical computation of experimental data according to kinetic hysteresis analysis.

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