Drug Interactions with Macrolide Antibiotics: Specificity of Pseudo-Suicide Inhibition and Induction of Cytochrome P-450
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.
KeywordsLiver Microsome Macrolide Antibiotic Liver Cytochrome Erythromycin Base Erythromycin Estolate
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