title: Plasma pharmacokinetics of ceftiofur metabolite desfuroylceftiofur cysteine disulfide in holstein steers: application of nonlinear mixed-effects modeling.
abstract: Eight clinically normal and drug-naïve Holstein steers were dosed with ceftiofur sodium at 2.2 mg/kg body weight intramuscularly. Doses were given at 24-h intervals for 5 days. Prior to the first dose and after all injections, blood samples were collected serially for determination of plasma concentrations of one of ceftiofur's main metabolites, desfuroylceftiofur cysteine disulfide (DCCD). A nonlinear mixed-effect model was used to analyze the plasma concentration data. A stochastic approximation expectation maximization (SAEM) algorithm in MONOLIX version 4.2.2 was used to approximate the likelihood of the nonlinear mixed-effect model and to estimate the population parameters. In addition, simulation studies were conducted to justify the model and demonstrate how to interpret the model parameters given different scenarios.
authors.affiliation: Office of Research, Division of Applied Veterinary Research, Center for Veterinary Medicine, U.S. Food and Drug Administration, Laurel, MD, USA.
authors.forename: O A
authors.initials: OA
authors.lastname: Chiesa
authors.affiliation: Office of Research, Division of Residue Chemistry, Center for Veterinary Medicine, U.S. Food and Drug Administration, Laurel, MD, USA.
authors.forename: S
authors.initials: S
authors.lastname: Feng
authors.affiliation: Office of Research, Division of Residue Chemistry, Center for Veterinary Medicine, U.S. Food and Drug Administration, Laurel, MD, USA.
authors.forename: P
authors.initials: P
authors.lastname: Kijak
authors.affiliation: Office of Research, Division of Applied Veterinary Research, Center for Veterinary Medicine, U.S. Food and Drug Administration, Laurel, MD, USA.
authors.forename: E A
authors.initials: EA
authors.lastname: Smith
authors.affiliation: Office of Research, Division of Residue Chemistry, Center for Veterinary Medicine, U.S. Food and Drug Administration, Laurel, MD, USA.
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.affiliation: Office of Biostatistics, Division I, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: J
authors.initials: J
authors.lastname: Qiu
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D002417:Cattle / Q000097:blood* / Q000378:metabolism; D002511:Cephalosporins / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics*; D003198:Computer Simulation; D008297:Male; D008954:Models, Biological; D012984:Software
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; C063324:desfuroylceftiofur; C053503:ceftiofur