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Zur Kenntnis der Pharmakokinetik von Cephalosporinen

Pharmacokinetic characteristics of cephalosporins

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Zusammenfassung

Die parenteral injizierbaren Cephalosporine Cephacetril, Cephalothin, Cephaloridin, Cefazolin, Cephradin und Cephapirin werden in ihrem pharmakokinetischen Verhalten beim Menschen untereinander anhand von Daten aus der Literatur und eigenen Messungen verglichen. Dabei werden die Löslichkeit in Wasser, die Serumkonzentration, die Harnausscheidung, die renale und totale Clearance, die Gallenausscheidung, die Metabolisierung, die Serumproteinbindung, die biologische Halbwertszeit und das Verteilungsvolumen besonders berücksichtigt. Es resultierte aus einer Pilot-Studie, daß, besonders in der ersten Stunde nach Gabe von 1 g i. v., das zu 87% proteingebundene Cefazolin niedrigere freie Wirkstoffkonzentrationen im Serum liefert als das zu 21% proteingebundene Cephacetril. Ein Vergleich zwischen Cephacetril, Cephalothin und Cephapirin zeigt, daß Cephacetril die höchsten Konzentrationen an freier Wirksubstanz im Serum aufweist. Die in der Pilot-Studie an drei Probanden gewonnenen Daten der Serumkonzentrationen von Cephacetril, Cefazolin und Cephadrin werden überdies mit einem Zwei-Kammermodell beschrieben.

Summary

The pharmacokinetic characteristics in man of the parenteral cephalosporins cephacetrile, cephalothin, cephaloridine, cefazolin, cephradine and cephapirin were compared by reference to data contained in the literature and on the basis of our own findings, special attention being paid to the following parameters: solubility in water, serum concentrations, urinary excretion, renal and total clearance, biliary excretion, metabolism, binding to serum proteins, biological half-life and distribution volume. A pilot study, in which the test substances were given intravenously in doses of 1 g, showed that during the first hour especially cephazoline, which in this experiment was bound to protein to the extent of 87 %, produces lower serum concentrations of free substance than cephacetrile, the binding value of which was 21%. A similar comparison between cephacetrile, cephalothin and cephapirin showed once again that it was cephacetrile which attained the highest serum concentrations of free active substance. In addition, the serum concentrations which cephacetrile, cefazolin, and cephradine attained in the three subjects studied in the pilot trial are described with the aid of a two-compartment model.

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Authors and Affiliations

  1. Pharma-Forschungslaboratorien, Ciba-Geigy AG, CH-4002, Basel

    H. G. Meyer-Brunot,  D. Randazzo &  W. Theobald

  2. Stellvertretender Leiter der Abteilung Klinische Pharmakologie, Departement für Innere Medizin der Universität, Kantonsspital, CH-4000, Basel

    P. Spring

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  1. H. G. Meyer-Brunot
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  3. W. Theobald
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Meyer-Brunot, H.G., Randazzo, D., Theobald, W. et al. Zur Kenntnis der Pharmakokinetik von Cephalosporinen. Infection 4 (Suppl 3), S181–S187 (1976). https://doi.org/10.1007/BF01781040

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