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

Mengjie Li, Ronette Gehring, Lisa A Tell, Ronald Baynes, Qingbiao Huang, Jim E. Riviere

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)4495-4503
Number of pages9
JournalAntimicrobial Agents and Chemotherapy
Volume58
Issue number8
DOIs
StatePublished - 2014

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Penicillin G
Swine
Pharmacokinetics
Food
Population
Anti-Bacterial Agents
Penicillins
Body Weight
Kidney
Muscles
Liver
Health
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology
  • Infectious Diseases

Cite this

Interspecies mixed-effect pharmacokinetic modeling of penicillin G in cattle and swine. / Li, Mengjie; Gehring, Ronette; Tell, Lisa A; Baynes, Ronald; Huang, Qingbiao; Riviere, Jim E.

In: Antimicrobial Agents and Chemotherapy, Vol. 58, No. 8, 2014, p. 4495-4503.

Research output: Contribution to journalArticle

Li, Mengjie ; Gehring, Ronette ; Tell, Lisa A ; Baynes, Ronald ; Huang, Qingbiao ; Riviere, Jim E. / Interspecies mixed-effect pharmacokinetic modeling of penicillin G in cattle and swine. In: Antimicrobial Agents and Chemotherapy. 2014 ; Vol. 58, No. 8. pp. 4495-4503.
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