Trimethoprim (
TMP) was administered in combination with either
sulphadiazine or sulphadimidine to broilers, and plasma concentrations were determined simultaneously by newly developed thin-layer and/or high-performance liquid-chromatographic procedures, which also allowed quantification of the N4-acetyl metabolites of the sulphonamides. After i.v. injection of
TMP (20 mg/kg body wt) and
sulphadiazine (100 mg/kg body wt), both compounds were rapidly eliminated from plasma with half-lives of 1 and 2.7 h, respectively. Apparent volumes of distribution (3.3 and 0.96 l/kg, respectively) indicated that the tissue distribution of
TMP was more extensive than that of the sulphonamide. After
oral administration of the same dosages, elimination appeared to be slower compared to the i.v. injection, but this was obviously related to delayed absorption. Bioavailability after
oral administration was approximately 100% of
sulphadiazine, but only about 60% for
TMP. Oral dosing of
TMP in combination with sulphadimidine yielded similar maximum plasma concentrations of both compounds to those obtained with the combination of
TMP with
sulphadiazine, but the plasma concentration decline of sulphadimidine appeared to be more rapid than that of
sulphadiazine after
oral administration. During prolonged administration of different dosages of
TMP-
sulphadiazine combinations via
drinking water, only low plasma concentrations were attained by the recommended dosage of the combination. Up to 10-fold higher dosages were tolerated by the animals without side-effects. In view of the fact that the sensitivity of bacterial strains to
TMP-sulphonamide combinations differs widely, the plasma concentrations determined in the present study during prolonged
drinking-water medication with different dosages of a
TMP-
sulphadiazine combination can be used to select effective doses for treatment of different
poultry diseases.