{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T17:57:26Z","timestamp":1769536646275,"version":"3.49.0"},"reference-count":50,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T00:00:00Z","timestamp":1769299200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002923","name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas","doi-asserted-by":"publisher","award":["PIP 2021-11220200101380CO"],"award-info":[{"award-number":["PIP 2021-11220200101380CO"]}],"id":[{"id":"10.13039\/501100002923","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Williams Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>Traditional macrolide antimicrobials are inhibitors of cytochrome P4503A (CYP3A) in cattle liver. Monensin (MON), an ionophore with a narrow safety margin, undergoes CYP3A-dependent O-demethylation, and its incompatibility with macrolides is well recognized in livestock animals. This study evaluated the effects of newer macrolides\u2014tilmicosin (TIL), tulathromycin (TUL), and gamithromycin (GAM)\u2014on CYP3A-dependent metabolism in bovine liver microsomes and examined how these drugs influence MON hepatic metabolism. Molecular docking studies were also performed to predict their interactions with CYP3A enzymes. The CYP3A-dependent enzyme activity, testosterone 6\u03b2-hydroxylase, was inhibited in the presence of triacetyl-oleandomycin (used as a reference macrolide), as well as with MON. None of the other macrolides tested affected this enzymatic activity. All macrolides inhibited MON metabolism, but the extent of inhibition observed with triacetyl-oleandomycin was higher than that produced by TIL, TUL, and GAM. Molecular docking analyses indicated that triacetyl-oleandomycin and MON exhibited the highest binding affinities for the active site of CYP3A isozymes, compared with TIL, TUL, and GAM. The agreement between enzymatic data and in silico predictions indicates that TIL, TUL, and GAM are weaker inhibitors of CYP3A-mediated MON metabolism. The modest reduction in MON hepatic metabolism caused by these macrolides\u2014commonly used in cattle feedlots\u2014suggests a low likelihood of clinically relevant drug\u2013drug interactions under typical dosing conditions.<\/jats:p>","DOI":"10.3390\/ani16030378","type":"journal-article","created":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T11:14:07Z","timestamp":1769426047000},"page":"378","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of Newer Veterinary Macrolide Antimicrobials on the CYP3A-Dependent Metabolism in Cattle Liver Microsomes: Potential Metabolic Drug\u2013Drug Interaction with Monensin"],"prefix":"10.3390","volume":"16","author":[{"given":"Paula","family":"Ichinose","sequence":"first","affiliation":[{"name":"Laboratorio de Farmacolog\u00eda, Centro de Investigaci\u00f3n Veterinaria de Tandil (CIVETAN), UNCPBA-CICPBA-CONICET, Campus Universitario, Tandil B7000, Buenos Aires, Argentina"},{"name":"Facultad de Ciencias Veterinarias, Universidad Nacional del Centro de la Provincia de Buenos Aires (UNCPBA), Campus Universitario, Tandil B7000, Buenos Aires, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan Pablo","family":"Munaf\u00f3","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Bioqu\u00edmicas de Bah\u00eda Blanca (INIBIBB-CONICET), Bah\u00eda Blanca B8000, Buenos Aires, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1526-5739","authenticated-orcid":false,"given":"Mar\u00eda Victoria","family":"Mir\u00f3","sequence":"additional","affiliation":[{"name":"Laboratorio de Farmacolog\u00eda, Centro de Investigaci\u00f3n Veterinaria de Tandil (CIVETAN), UNCPBA-CICPBA-CONICET, Campus Universitario, Tandil B7000, Buenos Aires, Argentina"},{"name":"Facultad de Ciencias Veterinarias, Universidad Nacional del Centro de la Provincia de Buenos Aires 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Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen","family":"Larsen","sequence":"additional","affiliation":[{"name":"Laboratorio de Farmacolog\u00eda, Centro de Investigaci\u00f3n Veterinaria de Tandil (CIVETAN), UNCPBA-CICPBA-CONICET, Campus Universitario, Tandil B7000, Buenos Aires, Argentina"},{"name":"Facultad de Ciencias Veterinarias, Universidad Nacional del Centro de la Provincia de Buenos Aires (UNCPBA), Campus Universitario, Tandil B7000, Buenos Aires, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2904-8820","authenticated-orcid":false,"given":"Carlos","family":"Lanusse","sequence":"additional","affiliation":[{"name":"Laboratorio de Farmacolog\u00eda, Centro de Investigaci\u00f3n Veterinaria de Tandil (CIVETAN), UNCPBA-CICPBA-CONICET, Campus Universitario, Tandil B7000, Buenos Aires, Argentina"},{"name":"Facultad de Ciencias Veterinarias, Universidad Nacional del Centro de la Provincia de Buenos Aires (UNCPBA), Campus Universitario, Tandil B7000, Buenos Aires, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7605-9744","authenticated-orcid":false,"given":"Adri\u00e1n","family":"Lifschitz","sequence":"additional","affiliation":[{"name":"Laboratorio de Farmacolog\u00eda, Centro de Investigaci\u00f3n Veterinaria de Tandil (CIVETAN), UNCPBA-CICPBA-CONICET, Campus Universitario, Tandil B7000, Buenos Aires, Argentina"},{"name":"Facultad de Ciencias Veterinarias, Universidad Nacional del Centro de la Provincia de Buenos Aires (UNCPBA), Campus Universitario, Tandil B7000, Buenos Aires, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0354-5001","authenticated-orcid":false,"given":"Guillermo","family":"Virkel","sequence":"additional","affiliation":[{"name":"Laboratorio de Farmacolog\u00eda, Centro de Investigaci\u00f3n Veterinaria de Tandil (CIVETAN), 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