Tiamulin selectively inhibits oxidative hepatic steroid and drug metabolism in vitro in the pig

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.     

The effect of flurbiprofen, a potent non-steroidal anti-inflammatory agent, upon Trypanosoma vivax infection in goats

Platelet aggregation leading to a decreased number of thrombocytes and reduced blood serotonin levels can be correlated with parasitaemia as has been observed in goats and cattle infected with T. vivax Y58. Flurbiprofen is a potent anti-inflammatory agent with antipyretic activity. In vitro , this agent inhibits platelet aggregation and blocks serotonin release. The results of the present study demonstrated that flurbiprofen inhibited the febrile reactions during the acute phase of T. vivax infection, but the drug did not prevent or reverse the associated drop in blood serotonin level during this period. Moreover, it was apparent that flurbiprofen had a deleterious effect on goats infected with T. vivax Y58. The infection in the untreated animals (sixteen out of seventeen goats) followed a rather mild and prolonged course with peaks of parasitaemia during the febrile episodes, whereas in flurbiprofen-treated goats (five animals), inoculated with the same number of trypanosomes, the parasitaemia was progressive and terminated in early death with disseminated intravascular coagulation at post mortem examination. These observations would seem to confirm the work of previous investigators, suggesting that anti-inflammatory agents have an aggravatory effect on the course of infection in animals inoculated with various strains of trypanosomes. Important differences exist, however, in the relationship between prostaglandin synthesis in the platelets of the goat and in those of other species.