Scientific Publications by FDA Staff

J Vet Pharmacol Ther 2016 Apr;39(2):149-56

Plasma pharmacokinetics of ceftiofur metabolite desfuroylceftiofur cysteine disulfide in holstein steers: application of nonlinear mixed-effects modeling.

Chiesa OA, Feng S, Kijak P, Smith EA, Li H, Qiu J

Eight clinically normal and drug-naive 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.