Cytochrome P-450 metabolic-intermediate complex formation and induction by macrolide antibiotics; a new class of agents.
1. By several criteria, macrolide antibiotics constitute a new class of nitrogenous cytochrome P-450 metabolic-intermediate complex-forming compounds. 2. Macrolide antibiotic metabolic-intermediate complexes are only formed in livers induced with phenobarbital or with the macrolide antibiotics themselves. The extent of metabolic-intermediate complex formation in microsomes from phenobarbital-induced rats is lower than that seen for members of the amphetamine and SKF 525-A classes of compounds. 3. Cytochrome P-450 induced by macrolide antibiotics, of which troleandomycin is the most potent, is extensively sequestered as a metabolic intermediate complex in vivo. 4. Cytochrome P-450 induced by troleandomycin differs, using several criteria, from those induced by phenobarbital, beta-naphthoflavone or SKF 525-A, and those present in uninduced rats.
D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism* / Q000494:pharmacology; D001571:Benzoflavones / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology; D011335:Proadifen / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D014217:Troleandomycin / Q000494:pharmacology; D019324:beta-Naphthoflavone
D000900:Anti-Bacterial Agents; D001571:Benzoflavones; D019324:beta-Naphthoflavone; D003577:Cytochrome P-450 Enzyme System; D011335:Proadifen; D014217:Troleandomycin; D010634:Phenobarbital