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

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

JOURNAL=Frontiers in Pharmacology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1378034

DOI=10.3389/fphar.2024.1378034

ISSN=1663-9812

ABSTRACT=<p><bold>Introduction:</bold> Streptococcus suis (<italic>S. suis</italic>) is a zoonotic pathogen threatening public health. Aditoprim (ADP), a novel veterinary medicine, exhibits an antibacterial effect against <italic>S. suis</italic>. In this study, a physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model was used to determine the dosage regimens of ADP against <italic>S. suis</italic> and withdrawal intervals.</p><p><bold>Methods:</bold> 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.</p><p><bold>Results:</bold> 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.</p><p><bold>Discussion:</bold> 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.</p>