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Tiamulin selectively inhibits oxidative hepatic steroid and drug metabolism in vitro in the pig
Author(s) -
WITKAMP R. F.,
NIJMEIJER S. M.,
MIERT A. S. J. P. A. M. VAN
Publication year - 1994
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/j.1365-2885.1994.tb00252.x
Subject(s) - tiamulin , pharmacology , hydroxylation , chemistry , drug metabolism , cytochrome p450 , biochemistry , microsome , cyp3a4 , demethylation , metabolism , biology , enzyme , antibiotics , gene , dna methylation , gene expression
The simultaneous use of the antibiotic tiamulin with certain ionophoric antibiotics (monensin, salinomycin) may give rise to a toxic interaction in pigs and poultry. In the present study, effects of tiamulin on hepatic cytochrome P450 activities in vitro were studied using pig liver microsomes. When tiamulin was added to the incubation medium the N‐demethylation rate of ethylmorphine and the hydroxylation of testosterone at the 6β‐ and 1 lα‐ positions was sirongly inhibited. Tiamulin inhibited these activities more than SKF525A or cimetidine, but less than ketoconazole. The microsomal N‐demethylation rate of erythromycin and the hydroxylation of testosterone at the 28‐ position were inhibited to a lesser degree, whereas the ethoxyresorufin‐O‐deethylation, aniline hydroxylation and testosterone hydroxylations at the 15α‐ and 15β‐ positions were not affected by tiamulin. No in vitro complexation by tiamulin of cytochrome P450 resulting in a loss of CO‐binding capacity could be demonstrated. Results from the present study suggest a selective inhibition of cytochrome P450 enzymes in pigs, probably belonging to the P4503A subfamily. The mechanism of this interaction is still unclear. However, interactions between tiamulin and those veterinary drugs or endogenous compounds which undergo oxidative metabolism by P450 enzymes must be considered. More research is needed to reveal which of the P450 enzymes are affected by tiamulin in order to improve the understanding and probably the predictability of this interaction.