Drug Interactions with Macrolide Antibiotics: Specificity of Pseudo-Suicide Inhibition and Induction of Cytochrome P-450

  • Patrick M. Dansette
  • Marcel Delaforge
  • Eric Sartori
  • Philippe Beaune
  • Maryse Jaouen
  • Daniel Mansuy
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 197)


Macrolide antibiotics like Erythromycin and Tri-acetyl oleandomycin (TAO) are metabolized to nitrosoderivatives which cause inactivation of Cytochrome P-450 by forming stable complex with the Iron of the hemoporphyrin. Several derivatives of erythromycin having lost their cladinose moiety are stronger inducer of liver cytochrome P-450 itself. The major form of cytochrome P-450 induced by all these macrolides in rat liver electrophoretically and immunogically indistiguishable from the major form induced by pregnenolone 16 ∝ carbonitrile (PCN). This form is particularly able to metabolize macrolide and to lead to the corresponding 456nm absorbing cytochrome P-4540 complexes in vivo and in vitro.


Liver Microsome Macrolide Antibiotic Liver Cytochrome Erythromycin Base Erythromycin Estolate 
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Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Patrick M. Dansette
    • 1
  • Marcel Delaforge
    • 1
  • Eric Sartori
    • 1
  • Philippe Beaune
    • 2
  • Maryse Jaouen
    • 1
  • Daniel Mansuy
    • 1
  1. 1.Laboratory of chemical and biochemical pharmacology and toxicologyCNRS UA400Paris Cedex 06France
  2. 2.Laboratory of BIochemistryCHU NeckerParis Cedex 15France

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