{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:29:37Z","timestamp":1785421777130,"version":"3.56.0"},"reference-count":39,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Laboratory of Infectious Animal Diseases, Antimicrobial Resistance, Veterinary Public Health and Food Chain Safety, University of Veterinary Medicine Budapest","award":["RRF-2.3.1-21-2022-00001"],"award-info":[{"award-number":["RRF-2.3.1-21-2022-00001"]}]},{"award":["RRF-2.3.1-21-2022-00001"],"award-info":[{"award-number":["RRF-2.3.1-21-2022-00001"]}],"id":[{"id":"https:\/\/ror.org\/03vayv672","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background: Assessment of antimicrobial exposure at the site of infection is essential for pharmacokinetic\/pharmacodynamic (PK\/PD)-guided antimicrobial therapy, yet plasma concentrations may not adequately reflect extracellular target-site exposure. This study characterized the pharmacokinetics of enrofloxacin and its active metabolite ciprofloxacin in plasma and interstitial fluid (ISF) following high-dose oral enrofloxacin administration in dogs and evaluated PK\/PD target attainment using nonlinear mixed-effects (NLME) modeling and Monte Carlo simulation. Methods: Nine healthy Beagle dogs were enrolled and received a single oral dose of enrofloxacin (target dose 20 mg\/kg). Following exclusion of one dog after vomiting, pharmacokinetic analyses included plasma data from eight dogs and interstitial fluid (ISF) data from six dogs. Serial plasma samples and protein-free ISF samples collected over 24 h by in vivo ultrafiltration were analyzed using LC\u2013MS\/MS. Non-compartmental and population pharmacokinetic analyses were performed separately for plasma and ISF data. Final population models were used to simulate 5000 virtual individuals for probability of target attainment (PTA) analyses across a range of minimum inhibitory concentrations (MICs) using established AUC0\u201324\/MIC and Cmax\/MIC targets. Results: Both enrofloxacin and ciprofloxacin exhibited delayed peak concentrations and greater overall exposure in ISF than in plasma. For enrofloxacin, mean AUC0\u201324 was higher in ISF than in plasma (44.9 vs. 21.6 \u00b5g \u00d7 h\/mL). Exploratory population pharmacokinetic models adequately described the plasma and ISF concentration-time data. Monte Carlo simulations showed consistently higher PTA in ISF than in plasma. For the more conservative AUC0\u201324\/MIC targets (\u2265100 and \u2265125), the MIC associated with \u226590% PTA for enrofloxacin was four-fold higher in ISF than in plasma (0.125 vs. 0.03 \u00b5g\/mL). Conclusions: High-dose oral enrofloxacin produced sustained extracellular exposure, resulting in more favorable PK\/PD target attainment in ISF than in plasma. These findings indicate that plasma pharmacokinetics alone may not accurately reflect target-site antimicrobial exposure and support further evaluation of ISF-based pharmacokinetic data for PK\/PD-guided optimization of fluoroquinolone therapy in dogs.<\/jats:p>","DOI":"10.3390\/antibiotics15080716","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T17:13:17Z","timestamp":1784826797000},"page":"716","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploratory Pharmacokinetic Characterization of Enrofloxacin and Ciprofloxacin in Plasma and Interstitial Fluid of Dogs: Nonlinear Mixed-Effects Modeling and PK\/PD Target Attainment Analysis"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-0236-4117","authenticated-orcid":false,"given":"Patrik","family":"Mag","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Veterinary Medicine Budapest, H-1078 Budapest, Hungary"},{"name":"National Laboratory of Infectious Animal Diseases, Antimicrobial Resistance, Veterinary Public Health and Food Chain Safety, University of Veterinary Medicine Budapest, H-1078 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zolt\u00e1n","family":"Somogyi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Veterinary Medicine Budapest, H-1078 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Kertenics","sequence":"additional","affiliation":[{"name":"Aurigon Labs Ltd., H-2120 Dunakeszi, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e1rton","family":"Kov\u00e1cs","sequence":"additional","affiliation":[{"name":"Research Center for Natural Sciences, Center for Structural Study, MS Metabolomics Laboratory, H-1117 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u00e1l","family":"Szab\u00f3","sequence":"additional","affiliation":[{"name":"Research Center for Natural Sciences, Center for Structural Study, MS Metabolomics Laboratory, H-1117 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3380-0827","authenticated-orcid":false,"given":"\u00c1kos","family":"Jerzsele","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Veterinary Medicine Budapest, H-1078 Budapest, Hungary"},{"name":"National Laboratory of Infectious Animal Diseases, Antimicrobial Resistance, Veterinary Public Health and Food Chain Safety, University of Veterinary Medicine Budapest, H-1078 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"dlad058","DOI":"10.1093\/jacamr\/dlad058","article-title":"Antimicrobial Stewardship in Veterinary Medicine: A Review of Online Resources","volume":"5","author":"Allerton","year":"2023","journal-title":"JAC Antimicrob. 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