A physiologically based pharmacokinetic model to optimize the dosage regimen and withdrawal time of cefquinome in pigs

Abstract

Cefquinome is widely used to treat respiratory tract diseases of swine. While extra-label dosages of cefquinome could improve clinical efficacy, they might lead to excessively high residues in animal-derived food. In this study, a physiologically based pharmacokinetic (PBPK) model was calibrated based on the published data and a microdialysis experiment to assess the dosage efficiency and food safety. For the microdialysis experiment, in vitro/in vivo relative recovery and concentration-time curves of cefquinome in the lung interstitium were investigated. This PBPK model is available to predict the drug concentrations in the muscle, kidney, liver, plasma, and lung interstitial fluid. Concentration-time curves of 1000 virtual animals in different tissues were simulated by applying sensitivity and Monte Carlo analyses. By integrating pharmacokinetic/pharmacodynamic target parameters, cefquinome delivered at 3–5 mg/kg twice daily is advised for the effective control of respiratory tract infections of nursery pig, which the bodyweight is around 25 kg. Based on the predicted cefquinome concentrations in edible tissues, the withdrawal interval is 2 and 3 days for label and the extra-label doses, respectively. This study provides a useful tool to optimize the dosage regimen of cefquinome against respiratory tract infections and predicts the concentration of cefquinome residues in edible tissues. This information would be helpful to improve the food safety and guide rational drug usage. Author summary Physiologically-based pharmacokinetic (PBPK) models, a mechanism-based model that incorporate physiological and chemical-specific parameters, can describe the absorption, distribution, metabolism and excretion of chemicals in different organs of animals. It can be applied for chemical risk assessment, dosage optimization and withdrawal intervals determination. The Extra-label use antimicrobial drug is a way to solve the treatment failure resulting from antimicrobial resistance. Integrate with pharmacokinetic/pharmacodynamic (PK/PD) parameters and maximum residual limit, PBPK model can determine a safe and effective dosage. This approach would be helpful to improve the food safety and guide rational drug usage.