In vitro metabolism of sulfathiazole in rumen fluid and its metabolism and disposition kinetics following intraruminal administration in sheep.

The antimicrobial agents may undergo a change in the complex stomach particularly in the rumen as a result of microbial fermentation in ruminants. Present investigation deals with the influence of ruminal fluid probably the role of ruminal microorganisms on the degradation of sulfathiazole in vitro and its metabolism and disposition following its single intraruminal administration (100 mg/kg) in adult german black head sheep. Sulfathiazole is metabolized to N4-acetyl sulfathiazole in the rumen fluid after its in vitro incubation at different concentrations (10-60 micrograms/ml) for varying time intervals (1-6 h) at a temperature of 38 +/- 0.5 degrees C. Likewise in vivo it is significantly metabolized to its N-acetyl metabolite in the rumen after an intraruminal administration. The levels of sulfathiazole are maintained above minimum effective therapeutic concentration (40 micrograms/ml) for more than 24 h in rumen fluid. The drug is poorly absorbed into the circulation after intraruminal administration since the levels in plasma could not reach up to minimum effective therapeutic concentration at any time. The biological half-life of sulfathiazole was found to be 16.7 h following single intraruminal administration. Results of this investigation suggest that oral or intraruminal application of sulfathiazole has only local effects in the rumen fluid. A systemic treatment is not possible after this path of application.