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

Autor: Yixing Lu, Liuye Yang, Wanying Zhang, Jie Li, Xianfeng Peng, Zonghua Qin, Zhenling Zeng, Dongping Zeng
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Frontiers in Veterinary Science, Vol 9 (2022)
Druh dokumentu: article
ISSN: 2297-1769
DOI: 10.3389/fvets.2022.1004248
Popis: This study aimed to evaluate the antibacterial activity of isopropoxy benzene guanidine (IBG) against C. perfringens based on pharmacokinetics/pharmacodynamics (PK/PD) modeling in broilers. The PK parameters of IBG in the plasma and ileal content of C. perfringens-infected broilers following oral administration at 2, 30, and 60 mg/kg body weight were investigated. in vivo PD studies were conducted over oral administration ranging from 2 to 60 mg/kg and repeated every 12 h for 3 days. The inhibitory Imax model was used for PK/PD modeling. Results showed that the MIC of IBG against C. perfringens was 0.5–32 mg/L. After oral administration of IBG, the peak concentration (Cmax), maximum concentration time (Tmax), 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 AUC0 − 24h/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 C. perfringens with MIC ≤ 2 mg/L. In addition, IBG showed potent activity against C. perfringens, 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 C. perfringens.
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