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

Abstract

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.

Chlorogenic acid protects against intestinal inflammation and injury by inactivating the mtDNA–cGAS–STING signaling pathway in broilers under necrotic enteritis challenge

“…However, the improper use of antibiotics results in drug resistance in C. perfringens and increases public concerns regarding residual drugs in animal products ( Derongs et al, 2020 ). This situation underscores an urgent need for a natural alternative in poultry production ( Lu et al, 2022 ).…”

Ex vivo pharmacokinetic/pharmacodynamic of hexahydrocolupulone against Clostridium perfringens in broiler chickens

“…The AUC 0-24h /MIC targets necessary to achieve bacteriostatic, bactericidal, and virtual eradication effects were determined to be 36.79, 52.67, and 62.71 h, respectively. To calculate the dosage, we multiplied the MIC distribution in MH broth by a scaling factor of 5.57 to account for the differences between MH and ileal content, and the Cl/F in ileal content was measured to be 28.01 ± 9.06 mL/kg h. The use of fu was not necessary for the utilization of PD data generated in the small intestine ( 32 ). The recommended therapeutic dosage of hexahydrocolupulone for the treatment of C. perfringens with an MIC of ≤4 mg/L was 32.9 mg/kg, to be administered every 24 h.…”

Metabolite Identification of Isopropoxy Benzene Guanidine in Rat Liver Microsomes by Using UHPLC-Q-TOF-MS/MS

“…Thus, guanidine has been developed as the dominant structural motif in the design of novel drugs for the treatment of various infectious diseases [ 30 , 31 ]. IBG is a substituted benzoguanidine derivative with good antibacterial activity against Gram-positive and Gram-negative bacteria [ 13 , 14 , 15 ]. The purpose of this work was to study the metabolism of IBG for the first time by using in vitro methods and analytical tools.…”

“…Guanidine-containing compounds also have good antibacterial activity against drug-resistant bacteria [ 10 , 11 ]. Isopropoxy benzene guanidine (IBG) is a novel guanidine compound that not only exhibits effective antibacterial activity against Gram-positive bacteria but also restores the sensitivity of Gram-negative bacteria to colistin as an antibiotic adjuvant [ 12 , 13 , 14 , 15 ]. IBG is expected to be a new antibacterial drug for bacterial infections.…”