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Antimicrob Agents Chemother. 2014 Aug;58(8):4495-503. doi: 10.1128/AAC.02806-14. Epub 2014 May 27.

Interspecies mixed-effect pharmacokinetic modeling of penicillin G in cattle and swine.

Author information

1
Institute of Computational Comparative Medicine, College of Veterinary Medicine, Kansas State University, Manhattan, Kansas, USA.
2
School of Veterinary Medicine, University of California, Davis, California, USA.
3
College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA.
4
Institute of Computational Comparative Medicine, College of Veterinary Medicine, Kansas State University, Manhattan, Kansas, USA jriviere@ksu.edu.

Abstract

Extralabel drug use of penicillin G in food-producing animals may cause an excess of residues in tissue which will have the potential to damage human health. Of all the antibiotics, penicillin G may have the greatest potential for producing allergic responses to the consumer of food animal products. There are, however, no population pharmacokinetic studies of penicillin G for food animals. The objective of this study was to develop a population pharmacokinetic model to describe the time-concentration data profile of penicillin G across two species. Data were collected from previously published pharmacokinetic studies in which several formulations of penicillin G were administered to diverse populations of cattle and swine. Liver, kidney, and muscle residue data were also used in this study. Compartmental models with first-order absorption and elimination were fit to plasma and tissue concentrations using a nonlinear mixed-effect modeling approach. A 3-compartment model with extra tissue compartments was selected to describe the pharmacokinetics of penicillin G. Typical population parameter estimates (interindividual variability) were central volumes of distribution of 3.45 liters (12%) and 3.05 liters (8.8%) and central clearance of 105 liters/h (32%) and 16.9 liters/h (14%) for cattle and swine, respectively, with peripheral clearance of 24.8 liters/h (13%) and 9.65 liters/h (23%) for cattle and 13.7 liters/h (85%) and 0.52 liters/h (40%) for swine. Body weight and age were the covariates in the final pharmacokinetic models. This study established a robust model of penicillin for a large and diverse population of food-producing animals which could be applied to other antibiotics and species in future analyses.

PMID:
24867969
PMCID:
PMC4136073
DOI:
10.1128/AAC.02806-14
[Indexed for MEDLINE]
Free PMC Article

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