AUTHOR=Lu Yixing , Yang Liuye , Zhang Wanying , Li Jie , Peng Xianfeng , Qin Zonghua , Zeng Zhenling , Zeng Dongping 

TITLE=Pharmacokinetics and pharmacodynamics of isopropoxy benzene guanidine against Clostridium perfringens in an intestinal infection model

JOURNAL=Frontiers in Veterinary Science

VOLUME=9

YEAR=2022

URL=https://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets.2022.1004248

DOI=10.3389/fvets.2022.1004248

ISSN=2297-1769

ABSTRACT=<p>This study aimed to evaluate the antibacterial activity of isopropoxy benzene guanidine (IBG) against <italic>C. perfringens</italic> based on pharmacokinetics/pharmacodynamics (PK/PD) modeling in broilers. The PK parameters of IBG in the plasma and ileal content of <italic>C. perfringens</italic>-infected broilers following oral administration at 2, 30, and 60 mg/kg body weight were investigated. <italic>in vivo</italic> PD studies were conducted over oral administration ranging from 2 to 60 mg/kg and repeated every 12 h for 3 days. The inhibitory <italic>I</italic><sub><italic>max</italic></sub> model was used for PK/PD modeling. Results showed that the MIC of IBG against <italic>C. perfringens</italic> was 0.5–32 mg/L. After oral administration of IBG, the peak concentration (<italic>C</italic><sub><italic>max</italic></sub>), maximum concentration time (<italic>T</italic><sub><italic>max</italic></sub>), and area under the concentration-time curve (AUC) in ileal content of broilers were 10.97–1,036.64 mg/L, 2.39–4.27 h, and 38.31–4,266.77 mg·h/L, respectively. After integrating the PK and PD data, the AUC<sub>0 − 24<italic>h</italic></sub>/MIC ratios needed for the bacteriostasis, bactericidal activity, and bacterial eradication were 4.00, 240.74, and 476.98 h, respectively. For dosage calculation, a dosage regimen of 12.98 mg/kg repeated every 12 h for 3 days was be therapeutically effective in broilers against <italic>C. perfringens</italic> with MIC ≤ 2 mg/L. In addition, IBG showed potent activity against <italic>C. perfringens</italic>, which may be responsible for cell membrane destruction. These results can facilitate the evaluation of the use of IBG in the treatment of intestinal diseases in broilers caused by <italic>C. perfringens</italic>.</p>