{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:23:52Z","timestamp":1787063032758,"version":"build-2736575974"},"reference-count":42,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,6,15]],"date-time":"2025-06-15T00:00:00Z","timestamp":1749945600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Secretar\u00eda de Ciencia y T\u00e9cnica, Universidad de Buenos Aires, Proyecto UBACyT","award":["20020220200090BA"],"award-info":[{"award-number":["20020220200090BA"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Veterinary Sciences"],"abstract":"<jats:p>The pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin, as well as the placental transfer of enrofloxacin and ciprofloxacin, have not been studied. The aims of this study were (1) to evaluate the pharmacokinetics of enrofloxacin and ciprofloxacin by intravenous and intramuscular administration of 7.5 mg\/kg in pregnant goats; (2) to determine the placental transfer of enrofloxacin and ciprofloxacin; (3) to conduct a PK\/PD analysis to calculate the PK\/PD cutoff of different dose regimens; and (4) to evaluate the tentative epidemiological cutoff values for coagulase-negative staphylococci wild-type isolates from goats. Plasmatic concentrations of enrofloxacin and ciprofloxacin in pregnant goats were well described by the parent\u2013metabolite model. Simultaneous modeling of enrofloxacin and ciprofloxacin in each individual allowed for a PK\/PD analysis that considered both drugs with antimicrobial activity. Our results show that both enrofloxacin and ciprofloxacin crossed the placenta in goats: fetal\/maternal concentration ratio were 0.58 \u00b1 0.05 and 0.03 \u00b1 0.01 for enrofloxacin and ciprofloxacin. MIC values of coagulase-negative staphylococci isolates (n = 90) were obtained, and tentative epidemiological cutoffs were calculated at 0.25 and 0.5 mg\/L for enrofloxacin and ciprofloxacin. According to PK\/PDco values, an intravenous dose regimen of 10 mg\/kg\/day was considered the most appropriate, but based on the PK\/PDco, culture, and AST data, an effective dosing regimen with the lowest possible dose could be selected to minimize the potential risk of fetal exposure to enrofloxacin.<\/jats:p>","DOI":"10.3390\/vetsci12060588","type":"journal-article","created":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T10:47:22Z","timestamp":1750070842000},"page":"588","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Pharmacokinetic and Pharmacodynamic Modeling of Enrofloxacin and Its Metabolite Ciprofloxacin in Pregnant Goats"],"prefix":"10.3390","volume":"12","author":[{"given":"Luis Adrian","family":"Ambros","sequence":"first","affiliation":[{"name":"C\u00e1tedra de Farmacolog\u00eda, Facultad de Ciencias Veterinarias, Universidad de Buenos Aires, Buenos Aires C.P. 1427, Argentina"},{"name":"Instituto en Investigaciones en Producci\u00f3n Animal (INPA), CONICET-Universidad de Buenos Aires, Buenos Aires C.P. 1427, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ver\u00f3nica","family":"Kreil","sequence":"additional","affiliation":[{"name":"C\u00e1tedra de Farmacolog\u00eda, Facultad de Ciencias Veterinarias, Universidad de Buenos Aires, Buenos Aires C.P. 1427, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Julio","family":"de Lucas Burneo","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda y Toxicolog\u00eda, Facultad de Veterinaria, Universidad Complutense de Madrid, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariano Guillermo","family":"Tinti","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias Agropecuarias, IRNASUS CONICET-Universidad Cat\u00f3lica de C\u00f3rdoba, C\u00f3rdoba X5016DHK, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1829-6113","authenticated-orcid":false,"given":"Manuel Ignacio","family":"San Andr\u00e9s Larrea","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda y Toxicolog\u00eda, Facultad de Veterinaria, Universidad Complutense de Madrid, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9799-4499","authenticated-orcid":false,"given":"Augusto Mat\u00edas","family":"Lorenzutti","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias Agropecuarias, IRNASUS CONICET-Universidad Cat\u00f3lica de C\u00f3rdoba, C\u00f3rdoba X5016DHK, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1111\/j.1365-2885.2009.01139.x","article-title":"Patient variation in veterinary medicine: Part I. Influence of altered physiological states","volume":"33","author":"Martinez","year":"2010","journal-title":"J. Vet. Pharmacol. Ther."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Costantine, M.M. (2014). Physiologic and pharmacokinetic changes in pregnancy. Front. Pharmacol., 5.","DOI":"10.3389\/fphar.2014.00065"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1053\/j.semperi.2015.08.003","article-title":"Pharmacokinetics of drugs in pregnancy","volume":"39","author":"Feghali","year":"2015","journal-title":"Semin. Perinatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1213\/ANE.0000000000001143","article-title":"Pharmacokinetics and pharmacodynamics of drugs commonly used in pregnancy and parturition","volume":"122","author":"Ansari","year":"2016","journal-title":"Anesth. Analg."},{"key":"ref_5","unstructured":"Mattison, D., and Halbert, L.A. (2021). Clinical Pharmacology During Pregnancy, Academic Press. [2nd ed.]."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/S0022-3565(24)39087-1","article-title":"Placental Transporters Relevant to Drug Distribution across the Maternal-Fetal Interface","volume":"294","author":"Ganapathy","year":"2000","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_7","first-page":"873","article-title":"New aspects in placental drug transfer","volume":"5","author":"Holcberg","year":"2003","journal-title":"IMAJ"},{"key":"ref_8","unstructured":"Riviere, J.E., and Papich, M.G. (2018). Fluoroquinolone antimicrobials drugs. Veterinary Pharmacology and Therapeutics, Wiley-Blackwell. [10th ed.]."},{"key":"ref_9","unstructured":"World Organisation for Animal Health (2025, February 20). OIE List of Antimicrobial Agents of Veterinary Importance. Available online: https:\/\/www.woah.org\/app\/uploads\/2021\/06\/a-oie-list-antimicrobials-june2021.pdf."},{"key":"ref_10","unstructured":"European Medicines Agency (2025, March 24). Committee for Medicinal Products for Veterinary Use (CVMP). EMA\/CVMP\/CHMP\/682198\/2017. Categorisation of Antibiotics in the European Union. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/report\/categorisation-antibiotics-european-union-answer-request-european-commission-updating-scientific_en.pdf."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1111\/evj.13044","article-title":"Diffusion of enrofloxacin to pregnancy fluids and effects on fetal cartilage after intravenous administration to late pregnant mares","volume":"51","author":"Ellerbrock","year":"2019","journal-title":"Equine Vet. J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.jpba.2005.07.021","article-title":"Kinetic disposition of lorazepam with focus on the glucuronidation capacity, transplacental transfer in parturients and racemization in biological samples","volume":"40","author":"Papini","year":"2006","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2175","DOI":"10.1128\/AAC.01017-09","article-title":"Pharmacokinetics of clindamycin in pregnant women in the peripartum period","volume":"54","author":"Muller","year":"2010","journal-title":"AAC"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.ijantimicag.2010.03.011","article-title":"Maternal and fetal blood levels of moxifloxacin, levofloxacin, cefepime and cefoperazone","volume":"36","author":"Ozyuncu","year":"2010","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_15","first-page":"77","article-title":"Transfer of ciprofloxacin, ofloxacin and levofloxacin across the perfused human placenta in vitro","volume":"61","author":"Polachek","year":"2006","journal-title":"OGS"},{"key":"ref_16","first-page":"64","article-title":"Pharmacokinetics of enrofloxacin after intravenous and intramuscular administration in Angora goats","volume":"65","author":"Elmas","year":"2001","journal-title":"Can. J. Vet. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1023\/A:1006481625615","article-title":"Pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin after intramuscular administration of enrofloxacin in goats","volume":"25","author":"Rao","year":"2001","journal-title":"Vet. Res. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/S0921-4488(02)00003-2","article-title":"Disposition kinetics of enrofloxacin and ciprofloxacin following intravenous administration of enrofloxacin in goats","volume":"44","author":"Rao","year":"2002","journal-title":"Small Rumin. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1053\/tvjl.2001.0594","article-title":"Pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin in goats given enrofloxacin alone and in combination with probenecid","volume":"163","author":"Rao","year":"2002","journal-title":"Vet. J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"77","DOI":"10.14405\/kjvr.2013.53.2.077","article-title":"Evaluation of bioequivalence of two enrofloxacin formulations after intramuscular administration in goats","volume":"53","author":"Aboubakr","year":"2013","journal-title":"Korean J. Vet. Res."},{"key":"ref_21","first-page":"293","article-title":"Disposition Kinetics of Enrofloxacin Following Intramuscular Administration in Goats","volume":"34","author":"Hussain","year":"2014","journal-title":"Pak. Vet. J."},{"key":"ref_22","first-page":"11","article-title":"Pharmacokinetics of enrofloxacin following intravenous and intramuscular administration in Kilis goats","volume":"2","author":"Demir","year":"2019","journal-title":"IJVAR"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/psp.2012.4","article-title":"Basic concepts in population modeling, simulation, and model-based drug development","volume":"1","author":"Mould","year":"2012","journal-title":"CPT Pharmacomet. Syst. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/psp.2013.14","article-title":"Basic concepts in population modeling, simulation, and model-based drug development\u2014Part 2: Introduction to pharmacokinetic modeling methods","volume":"2","author":"Mould","year":"2013","journal-title":"CPT Pharmacomet. Syst. Pharmacol."},{"key":"ref_25","first-page":"119","article-title":"Pharmacokinetics of enrofloxacin after single intravenous and intramuscular administration in young domestic ostrich (Struthio camelus)","volume":"27","author":"Rodriguez","year":"2004","journal-title":"JVPT"},{"key":"ref_26","unstructured":"(2018). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically, 11th ed. (Standard No. CLSI Standard M07)."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1111\/j.1469-0691.2006.01377.x","article-title":"Statistical characterisation of bacterial wild-type MIC value distributions and the determination of epidemiological cut-off values","volume":"12","author":"Turnidge","year":"2006","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1642","DOI":"10.1111\/bcp.14278","article-title":"A population pharmacokinetic model for escitalopram and its major metabolite in depressive patients during the perinatal period: Prediction of infant drug exposure through breast milk","volume":"86","author":"Weisskopf","year":"2020","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_29","first-page":"39","article-title":"Pharmacokinetic\/pharmacodynamic evaluation of marbofloxacin as a single injection for Pasteurellaceae respiratory infections in cattle using population pharmacokinetics and Monte Carlo simulations","volume":"41","author":"Paulin","year":"2018","journal-title":"JVPT"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1111\/evj.13385","article-title":"Determination of the pharmacokinetic-pharmacodynamic cut-off values of marbofloxacin in horses to support the establishment of a clinical breakpoint for antimicrobial susceptibility testing","volume":"53","author":"Schneider","year":"2021","journal-title":"Equine Vet. J."},{"key":"ref_31","first-page":"171","article-title":"Mathematical modeling and simulation in animal health. Part III: Using nonlinear mixed-effects to characterize and quantify variability in drug pharmacokinetics","volume":"41","author":"Bon","year":"2018","journal-title":"JVPT."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/S0924-8579(99)00146-6","article-title":"Intravenous pharmacokinetics of ciprofloxacin in goats","volume":"15","author":"Gorla","year":"2000","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1111\/j.1365-2885.2004.00605.x","article-title":"Plasma clearance","volume":"27","author":"Toutain","year":"2004","journal-title":"J. Vet. Pharmacol. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"241","DOI":"10.4142\/jvs.2008.9.3.241","article-title":"Disposition kinetics and urinary excretion of ciprofloxacin in goats following single intravenous administration","volume":"9","author":"Raina","year":"2008","journal-title":"J. Vet. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"670.e1","DOI":"10.1016\/j.ajog.2021.05.032","article-title":"Therapeutic concentration of ciprofloxacin and transfer across the human term placenta","volume":"225","author":"Noergaard","year":"2021","journal-title":"AJOG"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/S0022-3565(24)34867-0","article-title":"Efflux transport of a new quinolone antibacterial agent, HSR-903, across the blood-brain barrier","volume":"290","author":"Murata","year":"1999","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Chen, M., Yang, Y., Ying, Y., Huang, J., Sun, M., Hong, M., Wang, H., Xie, S., and Chen, D. (2023). ABC transporters and CYP3A4 mediate drug interactions between enrofloxacin and salinomycin leading to increased risk of drug residues and resistance. ABX, 12.","DOI":"10.3390\/antibiotics12020403"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.reprotox.2006.01.007","article-title":"P-glycoprotein in the placenta: Expression, localization, regulation and function","volume":"22","author":"Pavek","year":"2006","journal-title":"Reprod. Toxicol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.tvjl.2007.01.020","article-title":"Placental transfer of etomidate in pregnant ewes after an intravenous bolus dose and continuous infusion","volume":"175","author":"Fresno","year":"2008","journal-title":"Vet. J."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1007\/s11095-008-9537-z","article-title":"BCRP\/ABCG2 in the placenta: Expression, function and regulation","volume":"25","author":"Mao","year":"2008","journal-title":"Pharm. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1016\/j.vetmic.2013.12.021","article-title":"Pharmacokinetic\u2013pharmacodynamic (PK\u2013PD) modeling and the rational selection of dosage regimes for the prudent use of antimicrobial drugs","volume":"171","author":"Papich","year":"2014","journal-title":"Vet. Microbiol."},{"key":"ref_42","unstructured":"(2013). Performances Standards for Antimicrobial Disk and Dilution Susceptibility Tests for Bacteria Isolated from Animals; Second Informational Supplement (Standard No. CLSI Document VET01-S2)."}],"container-title":["Veterinary Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2306-7381\/12\/6\/588\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:52:19Z","timestamp":1760032339000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2306-7381\/12\/6\/588"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,15]]},"references-count":42,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["vetsci12060588"],"URL":"https:\/\/doi.org\/10.3390\/vetsci12060588","relation":{},"ISSN":["2306-7381"],"issn-type":[{"value":"2306-7381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,15]]}}}