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  • Title: Determination of free extracellular concentrations of piperacillin by microdialysis.
    Author: Nolting A, Costa TD, Vistelle R, Rand KH, Derendorf H.
    Journal: J Pharm Sci; 1996 Apr; 85(4):369-72. PubMed ID: 8901070.
    Abstract:
    The tissue penetration and distribution of antibiotics is of great importance, since most of the infections occur in the tissue. At the infection site, the free, unbound fraction of the antibiotic is responsible for the antiinfective effect. These free extracellular concentrations can be measured by microdialysis. It was the aim of the study to correlate free levels of the beta-lactam antibiotic piperacillin in blood with those in tissue. In vivo microdialysis sampling was used to study the tissue distribution patterns of piperacillin in anesthetized rats after single dose iv administration of the drug. The pharmacokinetics of piperacillin in plasma were consistent with a two-compartment body model. Comparisons between calculated free concentrations in the peripheral compartment and measured free extracellular concentrations revealed excellent agreement. Microdialysis is a suitable method to evaluate unbound drug concentrations in the tissues. In case of piperacillin, predictions of the concentration time profiles of free drug in the peripheral compartment can be made on the basis of plasma data.
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