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Pharmacological properties of cephalosporins

Pharmakologische Eigenschaften der Cephalosporine

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Summary

The cephalosporins differ in the substituents attached at the 3 and/or 7 positions of the molecule. Very schematically, substitution at C3 mainly modifies the overall pharmacokinetic properties whereas substitution at position 7 influences the antibacterial characteristics. When using the more common “generation” system for classification, three generations can be distinguished on the basis of their antibacterial spectrum, potency, and their stability to beta-lactamases. The first generation cephalosporins have similar antibacterial and pharmacokinetic characteristics. C3-esterified cephalosporins (e. g. cephalothin and cephapirin) are significantly metabolized. The so-called second generation cephalosporins exhibit only minor differences with respect to the pharmacokinetic properties in contrast to the third generation cephalosporins. The apparent volumes of distribution of most cephalosporins range between seven and 20 1, indicating that they mainly stay in the extracellular space. Plasma protein binding is variable from compound to compound. Generally, the major route of elimination of most cephalosporins is via the kidney except for cefoperazone and ceftriaxone which are both excreted to a large extent by the biliary route. With the exception of cefonicid, cefotetan and ceftriaxone, which have longer elimination half-lives (i.e. 4.5, 3.5 and around eight hours), all other cephalosporins have a half-life ranging from 0.5 to 2.5 hours. The pattern of adverse reactions is comparable for all the cephalosporins although there are slight differences in both the incidence and the type of reactions. The major categories of adverse reactions are gastrointestinal, dermatologic, hypersensitivity, haematologic, hepatic, renal as well as CNS effects. Alcohol intolerance (antabus-like effect) can occur when cephalosporins containing the NMTT moiety are administered concomitantly. Cephalosporins with either a NMTT or a MTD (methylthiadiazole) moiety are linked with hypoprothrombinaemias.

Zusammenfassung

Die Cephalosporine unterscheiden sich hinsichtlich der Substituenten in den Positionen 3 und 7 des Moleküls. Etwas vereinfacht dargestellt beeinflußt der Substituent in Position 3 überwiegend die pharmakokinetischen Eigenschaften und der Substituent in Position 7 die antibakteriellen Eigenschaften. Es gibt verschiedene Möglichkeiten, die heute verfügbaren Cephalosporine zu klassifizieren. Verwendet man die gebräuchliche Einteilung in Generationen, so lassen sich aufgrund des Wirkspektrums, der Wirkungsintensität sowie der Stabilität gegen Betalaktamasen drei Generationen unterscheiden. Die Vertreter der sog. ersten und zweiten Generation sind hinsichtlich der antibakteriellen und pharmakokinetischen Eigenschaften untereinander sehr ähnlich. Die Vertreter der sog. dritten Generation unterscheiden sich erheblich hinsichtlich ihrer pharmakokinetischen Eigenschaften. Die scheinbaren Verteilungsvolumina der meisten Cephalosporine liegen bei 7 bis 20 1. Dies ist ein Hinweis darauf, daß sie sich vor allem im Extrazellulärraum aufhalten. Im allgemeinen werden die Cephalosporine überwiegend renal ausgeschieden. Cefoperazon und Ceftriaxon werden auch in beachtlichem Umfang auf hepatobiliärem Weg ausgeschieden. Die Serumhalbwertszeiten der meisten Cephalosporine liegen in einem Bereich von 0,5 bis 2,5 Stunden, mit Ausnahme des Cefonicids, Cefotetans und Ceftriaxons, die längere Halbwertszeiten haben. Das Nebenwirkungsprofil der Cephalosporine ist für die einzelnen Substanzen sehr ähnlich. Einige Cephalosporine, die eine NMTT-Seitenkette in Position 3 besitzen, können Alkoholunverträglichkeitsreaktionen verursachen. Sowohl Cephalosporine mit einem NMTT- als auch mit einem MTD-(Methylthiadiazol-)Substituenten können durch Beeinflussung der Prothrombin-Biosythese Anlaß zu humoralen Blutgerinnungsstörungen sein.

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  1. Institut für Arzneimittel des Bundesgesundheitsamtes, Seestr. 10, W-1000, Berlin 65, Germany

    W. Christ (Dipl.-Chem.)

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Christ, W. Pharmacological properties of cephalosporins. Infection 19 (Suppl 5), S244–S252 (1991). https://doi.org/10.1007/BF01645535

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