In vitro formation of metabolic-intermediate cytochrome P450 complexes in rabbit liver microsomes by tiamulin and various macrolidesMonica Carlettia, Federica Gussona, Anna Zaghinib, Mauro Dacastoa, Luigi Marvasib and Carlo Nebbiaa
a Department of Animal Pathology, Division of Pharmacology and Toxicology, University of Turin, Grugliasco, Torino, Italy
b Department of Veterinary Public Health and Animal Pathology, University of Bologna, Ozzano Emilia, Bologna, Italy
(Received 6 December 2002, accepted 20 February 2003)
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 roxithromycin 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.
Key words: tiamulin / macrolide / rabbit / metabolic-intermediate complex / in vitro
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