Plasma disposition and tolerance of aditoprim in horses after single intravenous injection

Aditoprim, a broad spectrum antimicrobial agent acting as a reversible dihydrofolate reductase inhibitor, was intravenously injected into four 12 to 24-year old horses at a dosage of 5 mg/kg b. w. Blood samples were collected over a 48-hour period after drug injection, and the separated plasma samples were assayed for aditoprim by high performance liquid chromatography. The body temperature, heart rate, respiration rate, and behaviour were recorded during the experiment. The bilirubin and urea concentrations were also determined in several plasma samples, and liver function tests were carried out. The concentrations of aditoprim in the plasma of horses were higher than the MIC of this drug against recently isolated pathogens for 6-13 h (Pasteurella haemolytica A 1) to 48 h (E. coli). The main pharmacokinetic characteristics of aditoprim in horses were: a large volume of distribution, reaching a mean value of 7.8 l/kg; a mean plasma clearance of 5.0 l/min; a plasma elimination half-life of 12 h. The clinical observations, blood chemistry, and liver function tests all demonstrated that the drug was well tolerated by the horses, although it was injected intravenously as a 25% solution. It was concluded that the 25% aditoprim injection solution could be used in horses without adverse effects at 5 mg/kg. Furthermore, aditoprim should demonstrate good antibacterial effects in horses when intravenously injected once a day.