| Article title |
In vitro formation of metabolic-intermediate cytochrome P450 complexes in rabbit livermicrosomes by tiamulin and various macrolides |
| Journal |
Veterinary Research 34(4);2003 |
| Year |
2003 |
| Pages |
405 - 411 |
| Language |
en |
| Copyright |
INRA,EDP Sciences |
| PDF document |
 Vet.Res._0928-4249_2003_34_4/Vet.Res._0928-4249_2003_34_4_ART0004.pdf |
| Abstract |
Tiamulin and a number of macrolides were evaluated as to their ability in formingmetabolic-intermediate (MI) complexes with cytochrome P450 in liver microsomes from rabbitsbred for meat production. Complex formation, which occurred only in preparations where theexpression of P450 3A was increased as the result of rifampicin pre-treatment and withdifferent kinetics, was in the order tiamulin erythromycin TAO roxithromycin tylosin and did not take place with tilmicosin and spiramycin. Mostof the tested compounds underwent an oxidative N-dealkylation and a good relationship couldbe found between the rate of N-dealkylase activity in induced preparations and the aptitudein generating MI complexes. Although the results from in vitro studies should be interpretedwith caution, it is suggested that the potential for in vivo drug interactions also exists inthe rabbit for tiamulin and for four out of the six tested macrolides. |
| Keywords |
tiamulin,macrolide,rabbit,metabolic-intermediate complex,in vitro |