Pharmacokinetics of sulphadoxine and trimethoprim in horses. Half‐life and volume of distribution of sulphadoxine and trimethoprim and cumulative excretion of [¹⁴C]‐trimethoprim

A proprietary combination product containing sulphadoxine and trimethoprim was administered to horses by intravenous injection. Protein‐binding of sulphadoxine was dependent on the concentration in plasma and decreased from 72% at 50 μg/ml to 14% at 450 μg/ml. Sulphadoxine is eliminated from plasma in accordance with a three compartment open model. The elimination half‐life was on average 14 h while the volume of distribution was found to be 0.39 1/kg. Trimethoprim was eliminated from plasma in accordance with a two compartment open model. The elimination half‐life was on an average 3 h. Experiments in which trimethoprim was administered alone showed that the elimination half‐life was not dependent on the simultaneous administration of sulphadoxine. About 50% of trimethoprim was bound to plasma proteins, but in contrast to sulphadoxine there was no dependence between plasma concentration and protein binding. The protein binding of trimethoprim was independent of the presence of sulphadoxine and vice versa. Experiments with 14 C‐labelled trimethoprim showed that it was excreted in almost equal amounts in urine and faeces. 97% of the administered dose was recovered in urine and faeces during the course of the first 4 days after administration.