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Studies on the toxic interaction between monensin and tiamulin in rats: effects on P450 activities
G Szücs1, P Laczay, J Bajnógel
1Department of Toxicology, EGIS Pharmaceuticals Ltd, H-1475 Budapest 10, P.O. Box 100, Hungary.
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 (monesin 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.
Insights
Tiamulin, but not monensin alone, induces liver enzymes in rats. When combined, tiamulin significantly enhances monensin
Area of Science:
- Pharmacology
- Biochemistry
- Toxicology
Background:
- Microsomal enzymes are crucial for drug metabolism.
- Monensin and tiamulin are veterinary antibiotics with potential interactions.
- Understanding these interactions is vital for safe drug use.
Purpose of the Study:
- To investigate the individual and combined effects of monensin and tiamulin on rat liver microsomal enzymes.
- To determine if tiamulin influences monensin's biotransformation.
- To assess potential sex-based differences in enzyme activity.
Main Methods:
- Rats were administered monensin and/or tiamulin at various doses.
- Effects on liver microsomal enzyme activities were measured.
- Enzyme induction and inhibition patterns were analyzed.
Main Results:
- Monensin alone showed minimal impact on liver enzymes.
- Tiamulin caused a dose-dependent induction of hepatic enzymes.
- Combined administration at low doses significantly elevated P450-related enzyme activities, more so in females.
Conclusions:
- Tiamulin induces liver microsomal enzymes in a dose-dependent manner.
- Simultaneous administration of tiamulin enhances monensin's effect on P450 enzymes.
- Tiamulin may alter monensin biotransformation, potentially increasing reactive metabolites.