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StudIES oN the Toxic Interaction between Monensin and Tiamulin in Rats: EFFECTS ON P450 ACTIVITIES

Author:
Szűcs, G., Laczay, P., Bajnógel, Judit, Móra, Zsuzsa
Source:
Acta veterinaria Hungarica 2000 v.48 no.3 pp. 361-368
ISSN:
0236-6290
Subject:
antibiotics, biotransformation, body weight, dose response, enzyme activity, enzymes, females, gene induction, liver, males, metabolites, monensin, rats, tiamulin, toxicity
Abstract:
Studies were carried out to investigate the effects of monensin and tiamulin, and the simultaneous administration of both compounds on microsomal enzymes in rats. In Phase I of the experiments the effects of monensin and tiamulin were studied separately (monensin 10, 30, and 50 mg/kg or tiamulin 40, 120, and 200 mg/kg body weight, respectively), while in Phase II the two compounds were administered simultaneously (monensin 10 mg/kg and tiamulin 40 mg/kg b.w., respectively). When monensin was administered by itself, it exerted no significant effect on microsomal liver enzymes. In a few cases, slight inhibition of certain enzyme activities was seen. Tiamulin provoked a dose-dependent hepatic enzyme induction. The combined administration of monensin and tiamulin at low doses (10 and 40 mg/kg, respectively) resulted in marked elevation of P450-related enzyme activities. The enzyme induction was more pronounced in females than in males. The results suggest that the simultaneous administration of tiamulin may influence the biotransformation of monensin, possibly increasing the amount of reactive metabolite(s) of the ionophore antibiotic.
Agid:
4796276