title: Plasma disposition of toltrazuril and its metabolites, toltrazuril sulfoxide and toltrazuril sulfone, in rabbits after oral administration.
abstract: The objective of this study was to evaluate the pharmacokinetic profiles of toltrazuril (TZR), and its major metabolites toltrazuril sulfoxide (TZR x SO) and toltrazuril sulfone (TZR x SO(2)) in rabbits after oral administrations. Rabbits were dosed once with 10 and 20mg/kg TZR via stomach tube with manual restraint. The plasma concentrations of TZR, TZR x SO and TZR x SO(2) 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 x SO and TZR x SO(2) were 30.2+/-1.5microg/mL at 20.0+/-6.9h, 8.9+/-1.3microg/mL at 20.0+/-6.9h and 14.7+/-3.9microg/mL at 96.0+/-0.0h after oral administration of TZR with 10mg/kg bw, respectively. The terminal elimination half-lives for TZR, TZR x SO and TZR x SO(2) after oral dose of 10mg/kg were 52.7+/-3.6, 56.1+/-10.7 and 76.7+/-7.5h, respectively. Plasma peak concentrations of TZR, TZR x SO and TZR x SO(2) were 39.4+/-1.2microg/mL at 28.0+/-6.9h, 12.5+/-3.9microg/mL at 20.0+/-6.9h and 24.9+/-8.74microg/mL at 112.0+/-6.9h after oral administration of TZR with 20mg/kg bw, respectively. The terminal elimination half-lives for TZR, TZR x SO and TZR x SO(2) after oral dose of 20mg/kg were 56.7+/-1.9, 68.8+/-12.5 and 82.3+/-12.6h, respectively. In conclusion, TZR was very well-absorbed through the gastrointestinal tract and rapidly metabolized to TZR x SO and TZR x SO(2) in rabbits after oral administration. TZR x SO(2) was actually more slowly eliminated than TZR and TZR x SO.
authors.affiliation: Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Myoung-Seok
authors.initials: MS
authors.lastname: Kim
authors.forename: Jong-Hwan
authors.initials: JH
authors.lastname: Lim
authors.forename: Youn-Hwan
authors.initials: YH
authors.lastname: Hwang
authors.forename: Byung-Kwon
authors.initials: BK
authors.lastname: Park
authors.forename: In-Bae
authors.initials: IB
authors.lastname: Song
authors.forename: Hyo-In
authors.initials: HI
authors.lastname: Yun
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D003049:Coccidiostats / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D006207:Half-Life; D008297:Male; D011817:Rabbits; D011897:Random Allocation; D014227:Triazines / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*
chemical_list: D003049:Coccidiostats; D014227:Triazines; C036670:toltrazuril