title: Pharmacokinetic modeling and Monte Carlo simulation of ondansetron following oral administration in dogs.
abstract: Ondansetron is a potent antiemetic drug that has been commonly used to treat acute and chemotherapy-induced nausea and vomiting (CINV) in dogs. The aim of this study was to perform a pharmacokinetic analysis of ondansetron in dogs following oral administration of a single dose. A single 8-mg oral dose of ondansetron (Zofran(®) ) was administered to beagles (n = 18), and the plasma concentrations of ondansetron were measured by liquid chromatography-tandem mass spectrometry. The data were analyzed by modeling approaches using ADAPT5, and model discrimination was determined by the likelihood-ratio test. The peak plasma concentration (Cmax ) was 11.5 ± 10.0 ng/mL at 1.1 ± 0.8 h. The area under the plasma concentration vs. time curve from time zero to the last measurable concentration was 15.9 ± 14.7 ng·h/mL, and the half-life calculated from the terminal phase was 1.3 ± 0.7 h. The interindividual variability of the pharmacokinetic parameters was high (coefficient of variation > 44.1%), and the one-compartment model described the pharmacokinetics of ondansetron well. The estimated plasma concentration range of the usual empirical dose from the Monte Carlo simulation was 0.1-13.2 ng/mL. These findings will facilitate determination of the optimal dose regimen for dogs with CINV.
authors.affiliation: College of Pharmacy, Kyungsung University, Nam-gu, Busan, South Korea.
authors.forename: I-H
authors.initials: IH
authors.lastname: Baek
authors.forename: B-Y
authors.initials: BY
authors.lastname: Lee
authors.forename: J
authors.initials: J
authors.lastname: Kang
authors.forename: K-I
authors.initials: KI
authors.lastname: Kwon
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000932:Antiemetics / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D004285:Dogs / Q000097:blood / Q000378:metabolism*; D006207:Half-Life; D008954:Models, Biological; D009010:Monte Carlo Method; D017294:Ondansetron / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D000932:Antiemetics; D017294:Ondansetron