Plasma disposition of toltrazuril and its metabolites, toltrazuril sulfoxide and toltrazuril sulfone, in rabbits after oral administration

The objective of this study was to evaluate the pharmacokinetic profiles of toltrazuril (TZR), and its major metabolites toltrazuril sulfoxide (TZR·SO) and toltrazuril sulfone (TZR·SO2) in rabbits after oral administrations. Rabbits were dosed once with 10 and 20 mg/kg TZR via stomach tube with manual restraint. The plasma concentrations of TZR, TZR·SO and TZR·SO2 were determined by liquid chromatography/mass spectrometry. Plasma concentration–time data after single oral administration were analyzed by a non-compartmental analysis. Plasma peak concentrations of TZR, TZR·SO and TZR·SO2 were 30.2 ± 1.5 μg/mL at 20.0 ± 6.9 h, 8.9 ± 1.3 μg/mL at 20.0 ± 6.9 h and 14.7 ± 3.9 μg/mL at 96.0 ± 0.0 h after oral administration of TZR with 10 mg/kg bw, respectively. The terminal elimination half-lives for TZR, TZR·SO and TZR·SO2 after oral dose of 10 mg/kg were 52.7 ± 3.6, 56.1 ± 10.7 and 76.7 ± 7.5 h, respectively. Plasma peak concentrations of TZR, TZR·SO and TZR·SO2 were 39.4 ± 1.2 μg/mL at 28.0 ± 6.9 h, 12.5 ± 3.9 μg/mL at 20.0 ± 6.9 h and 24.9 ± 8.74 μg/mL at 112.0 ± 6.9 h after oral administration of TZR with 20 mg/kg bw, respectively. The terminal elimination half-lives for TZR, TZR·SO and TZR·SO2 after oral dose of 20 mg/kg were 56.7 ± 1.9, 68.8 ± 12.5 and 82.3 ± 12.6 h, respectively. In conclusion, TZR was very well-absorbed through the gastrointestinal tract and rapidly metabolized to TZR·SO and TZR·SO2 in rabbits after oral administration. TZR·SO2 was actually more slowly eliminated than TZR and TZR·SO.