Frontiers in Pharmacology (Apr 2024)

A physiologically based pharmacokinetic/pharmacodynamic model to determine dosage regimens and withdrawal intervals of aditoprim against Streptococcus suis

  • Kun Mi,
  • Kun Mi,
  • Lei Sun,
  • Lei Sun,
  • Lan Zhang,
  • Lan Zhang,
  • Aoran Tang,
  • Aoran Tang,
  • Xiaoyuan Tian,
  • Xiaoyuan Tian,
  • Yixuan Hou,
  • Yixuan Hou,
  • Lingling Sun,
  • Lingli Huang,
  • Lingli Huang,
  • Lingli Huang

DOI
https://doi.org/10.3389/fphar.2024.1378034
Journal volume & issue
Vol. 15

Abstract

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Introduction: Streptococcus suis (S. suis) is a zoonotic pathogen threatening public health. Aditoprim (ADP), a novel veterinary medicine, exhibits an antibacterial effect against S. suis. In this study, a physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model was used to determine the dosage regimens of ADP against S. suis and withdrawal intervals.Methods: The PBPK model of ADP injection can predict drug concentrations in plasma, liver, kidney, muscle, and fat. A semi-mechanistic pharmacodynamic (PD) model, including susceptible subpopulation and resistant subpopulation, is successfully developed by a nonlinear mixed-effect model to evaluate antibacterial effects. An integrated PBPK/PD model is conducted to predict the time-course of bacterial count change and resistance development under different ADP dosages.Results: ADP injection, administrated at 20 mg/kg with 12 intervals for 3 consecutive days, can exert an excellent antibacterial effect while avoiding resistance emergence. The withdrawal interval at the recommended dosage regimen is determined as 18 days to ensure food safety.Discussion: This study suggests that the PBPK/PD model can be applied as an effective tool for the antibacterial effect and safety evaluation of novel veterinary drugs.

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