{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T14:05:01Z","timestamp":1784297101093,"version":"3.55.0"},"reference-count":68,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T00:00:00Z","timestamp":1619049600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National key research and development program","award":["2016YFD0501310"],"award-info":[{"award-number":["2016YFD0501310"]}]},{"name":"National key research and development program","award":["2018YFD0500301"],"award-info":[{"award-number":["2018YFD0500301"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Zoonotic intestinal pathogens threaten human health and cause huge economic losses in farming. Enrofloxacin (ENR) shows high antibacterial activity against common intestinal bacteria. However, its poor palatability and low aqueous solubility limit the clinical application of ENR. To obtain an ENR oral preparation with good palatability and high solubility, a granule containing an amorphous ENR solid dispersion (ENR-SD) was prepared. Meanwhile, a PBPK model of ENR in pigs was built based on the physiological parameters of pigs and the chemical-specific parameters of ENR to simulate the pharmacokinetics (PK) of ENR-SD granules in the intestinal contents. According to the results of parameter sensitivity analysis (PSA) and the predicted PK parameters at different doses of the model, formulation strategies and potential dose regimens against common intestinal infections were provided. The DSC and XRD results showed that no specific interactions existed between the excipients and ENR during the compatibility tests, and ENR presented as an amorphous form in ENR-SD. Based on the similar PK performance of ENR-SD granules and the commercial ENR soluble powder suggesting continued enhancement of the solubility of ENR, a higher drug concentration in intestinal contents could not be obtained. Therefore, a 1:5 ratio of ENR and stearic acid possessing a saturated aqueous solubility of 1190 \u00b1 7.71 \u00b5g\/mL was selected. The predictive AUC24h\/MIC90 ratios against Campylobacter jejuni, Salmonella, and Escherichia coli were 133, 266 and 8520 (&gt;100), respectively, suggesting that satisfactory efficacy against common intestinal infections would be achieved at a dose of 10 mg\/kg b.w. once daily. The PSA results indicated that the intestinal absorption rate constant (Ka) was negatively correlated with the Cmax of ENR in the intestine, suggesting that we could obtain higher intestinal Cmax using P-gp inducers to reduce Ka, thus obtaining a higher Cmax. Our studies suggested that the PBPK model is an excellent tool for formulation and dose design.<\/jats:p>","DOI":"10.3390\/pharmaceutics13050602","type":"journal-article","created":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T13:59:14Z","timestamp":1619099954000},"page":"602","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Application of a Physiologically Based Pharmacokinetic Model to Develop a Veterinary Amorphous Enrofloxacin Solid Dispersion"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1411-9531","authenticated-orcid":false,"given":"Kaixiang","family":"Zhou","sequence":"first","affiliation":[{"name":"National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meixia","family":"Huo","sequence":"additional","affiliation":[{"name":"National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjin","family":"Ma","sequence":"additional","affiliation":[{"name":"National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7058-1849","authenticated-orcid":false,"given":"Kun","family":"Mi","sequence":"additional","affiliation":[{"name":"National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangyue","family":"Xu","sequence":"additional","affiliation":[{"name":"National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samah Attia","family":"Algharib","sequence":"additional","affiliation":[{"name":"National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Department of Clinical Pathology, Faculty of Veterinary Medicine, Benha University, Moshtohor, Toukh 13736, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyu","family":"Xie","sequence":"additional","affiliation":[{"name":"National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingli","family":"Huang","sequence":"additional","affiliation":[{"name":"National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"28","DOI":"10.3201\/eid0501.990104","article-title":"Campylobacter jejuni\u2014An emerging foodborne pathogen","volume":"5","author":"Altekruse","year":"1999","journal-title":"Emerg. 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