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

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 concent...

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Bibliographic Details
Published in:Journal of veterinary pharmacology and therapeutics 2016-04, Vol.39 (2), p.149-156
Main Authors: Chiesa, O. A., Feng, S., Kijak, P., Smith, E. A., Li, H., Qiu, J.
Format: Article
Language:English
Subjects:
Animals
Anti-Bacterial Agents - blood
Anti-Bacterial Agents - metabolism
Anti-Bacterial Agents - pharmacokinetics
Cattle - blood
Cattle - metabolism
Cephalosporins - blood
Cephalosporins - metabolism
Cephalosporins - pharmacokinetics
Computer Simulation
Male
Models, Biological
Software
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Summary: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.
ISSN:0140-7783
1365-2885
DOI:10.1111/jvp.12245