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

• Published in: PLoS computational biology 2023-08, Vol.19 (8), p.e1011331-e1011331
• Main Authors: Mi, Kun, Sun, Lei, Hou, Yixuan, Cai, Xin, Zhou, Kaixiang, Ma, Wenjin, Xu, Xiangyue, Pan, Yuanhu, Liu, Zhenli, Huang, Lingli
• Format: Article
• Language: English
• Subjects: Analysis; Animal tissues; Animal-based foods; Biology and Life Sciences; Calibration; Contamination; Dialysate; Dosage; Dosage and administration; Drug dosages; Drug resistance; Drug withdrawal; Food; Food safety; Hogs; Kidneys; Labels; Liver; Lungs; Mandatory drug testing; Medical research; Medicine and Health Sciences; Medicine, Experimental; Microdialysis; Monte Carlo simulation; Parameter sensitivity; Pathogens; Pharmacodynamics; Pharmacokinetics; Pharmacology; Physiology; Plasma; Regression analysis; Research and Analysis Methods; Residues; Respiration; Respiratory tract; Respiratory tract diseases; Respiratory tract infection; Safety and security measures; Sensitivity analysis; Simulation; Swine; Veterinary drugs
• ISSN: 1553-7358; 1553-734X; 1553-7358
• DOI: 10.1371/journal.pcbi.1011331

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.