Pharmacokinetics and Metabolism of Toltrazuil and Its Major Metabolites after Oral Administration in Broilers

Abstract

Toltrazuril is a symmetrical tiazinetrione compound. It is active against all intracellular developmental stages including those of schizogony and gametogony. In this study the disposition kinetics of toltrazuril (TZR) and its major metabolites (TZR-SO and TZR-SO₂) in broiler chickens after single oral administrations of 10 or 20 mg/kg were investigated. Mean plasma concentrations of TZR peaked at 16.4 and 25.2 μg/mL at 5.0 and 4.7 h after dosing, respectively. TZR was converted to the short-lived intermediary metabolite toltrazuril sulfoxide (TZR-SO), and then further metabolized to the reactive toltrazuril sulfone (TZR-SO₂) being actually more slow eliminated with 80.3 and 82.9 h than TZR (10.6 and 10.7 h) or TZR-SO (14.8 and 15.3 h) in low and high dosing groups, respectively. Prolonged elimination half-life of TZR-SO₂ could be interpreted as the persistent clinical efficacy of TZR in the treatment of protozoal parasites infection.