title: In vitro formation of metabolic-intermediate cytochrome P450 complexes in rabbit liver microsomes by tiamulin and various macrolides.
abstract: Tiamulin and a number of macrolides were evaluated as to their ability in forming metabolic-intermediate (MI) complexes with cytochrome P450 in liver microsomes from rabbits bred for meat production. Complex formation, which occurred only in preparations where the expression of P450 3A was increased as the result of rifampicin pre-treatment and with different kinetics, was in the order tiamulin > erythromycin > TAO approximately roxithromycin approximately tylosin and did not take place with tilmicosin and spiramycin. Most of the tested compounds underwent an oxidative N-dealkylation and a good relationship could be found between the rate of N-dealkylase activity in induced preparations and the aptitude in generating MI complexes. Although the results from in vitro studies should be interpreted with caution, it is suggested that the potential for in vivo drug interactions also exists in the rabbit for tiamulin and for four out of the six tested macrolides.
authors.affiliation: Department of Animal Pathology, Division of Pharmacology and Toxicology, University of Turin, Grugliasco, Torino, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Carletti
authors.forename: Federica
authors.initials: F
authors.lastname: Gusson
authors.forename: Anna
authors.initials: A
authors.lastname: Zaghini
authors.forename: Mauro
authors.initials: M
authors.lastname: Dacasto
authors.forename: Luigi
authors.initials: L
authors.lastname: Marvasi
authors.forename: Carlo
authors.initials: C
authors.lastname: Nebbia
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000378:metabolism*; D004224:Diterpenes / Q000494:pharmacology*; D004917:Erythromycin / Q000494:pharmacology; D007700:Kinetics; D018942:Macrolides / Q000494:pharmacology*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism; D011817:Rabbits / Q000378:metabolism*; D015572:Spiramycin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D004224:Diterpenes; D018942:Macrolides; D004917:Erythromycin; D015572:Spiramycin; D003577:Cytochrome P-450 Enzyme System; C014224:tiamulin; D010089:Oxidoreductases, N-Demethylating