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Apply a Physiologically Based Pharmacokinetic Model to Promote the Development of Enrofloxacin Granules: Predict Withdrawal Interval and Toxicity Dose

Authors :
Kaixiang Zhou
Aimei Liu
Wenjin Ma
Lei Sun
Kun Mi
Xiangyue Xu
Samah Attia Algharib
Shuyu Xie
Lingli Huang
Source :
Antibiotics, Vol 10, Iss 8, p 955 (2021)
Publication Year :
2021
Publisher :
MDPI AG, 2021.

Abstract

Enrofloxacin (ENR) granules were developed to prevent and control the infections caused by foodborne zoonotic intestinal pathogens in our previous studies. To promote the further development of ENR granules and standardize their usage in pigs, a physiologically based pharmacokinetic (PBPK) model of the ENR granule in pigs was built to determine the withdrawal time (WT) and evaluate the toxicity to pigs. Meanwhile, the population WT was determined by a Monte Carlo analysis to guarantee pork safety. The fitting results of the model showed that the tissue residual concentrations of ENR, ciprofloxacin, and ENR plus ciprofloxacin were all well predicted by the built PBPK model (R2 > 0.82). When comparing with the EMA’s WT1.4 software method, the final WT (6 d) of the ENR granules in the population of pigs was well predicted. Moreover, by combining the cytotoxicity concentration (225.9 µg/mL) of ENR against pig hepatocytes, the orally safe dosage range (≤130 mg/kg b.w.) of the ENR granules to pigs was calculated based on the validated PBPK model. The well-predicted WTs and a few uses in animals proved that the PBPK model is a potential tool for promoting the judicious use of antimicrobial agents and evaluating the toxicity of the veterinary antimicrobial products.

Details

Language :
English
ISSN :
20796382
Volume :
10
Issue :
8
Database :
Directory of Open Access Journals
Journal :
Antibiotics
Publication Type :
Academic Journal
Accession number :
edsdoj.64220330fcdf489391faefd1ea05b4df
Document Type :
article
Full Text :
https://doi.org/10.3390/antibiotics10080955