{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T11:27:45Z","timestamp":1770550065610,"version":"3.49.0"},"reference-count":16,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"content-version":"vor","delay-in-days":20,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Manipulation of forms of rectally administered metronidazole to improve bioavailability in horses has not been reported.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Hypothesis\/Objectives<\/jats:title>\n                    <jats:p>Evaluate the pharmacokinetics of 3 rectal metronidazole preparations compared to nasogastric (NG) administration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Animals<\/jats:title>\n                    <jats:p>Seven healthy horses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Phase 1A was a randomized, 3-way crossover, single-dose pharmacokinetic study, and Phases 1B and 2 were non-randomized, single-dose follow-up studies. Metronidazole (20\u00a0mg\/kg) was administered NG and rectally in water (RW20), as a rectal gel (RG), and in dimethyl sulfoxide (DMSO). Metronidazole (80\u00a0mg\/kg) was also administered rectally in water (RW80) to 3 horses. Plasma concentrations were measured using liquid chromatography\/tandem mass spectrometry. Pharmacokinetic variables were calculated, and predicted steady-state area under the curve (AUC0-24,ss) to minimum inhibitory concentration ratio was used as a pharmacodynamic target.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Bioavailabilities for RW20 (33.7%), RG (2.49%), and DMSO (12.0%) were low relative to NG administration. When administered at a dosage of 20\u00a0mg\/kg, only NG every 8\u00a0h was predicted to achieve the pharmacodynamic target in all horses. Administered rectally in water, the metronidazole maximum concentration increased from 3.11 +\/\u2212 0.63\u00a0\u03bcg\/mL to 4.19 +\/\u2212 1.04\u00a0\u03bcg\/mL when the dose was increased to 80\u00a0mg\/kg. The RW80 predicted AUC0-24,ss for every 8\u00a0h administration was above target for all 3 horses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and clinical importance<\/jats:title>\n                    <jats:p>With the tested preparations, rectal administration of metronidazole at a standard dosage of 20\u00a0mg\/kg yielded subtherapeutic plasma concentrations. Administering a 4-fold higher dose rectally in water might overcome these limitations. Oral and intravenous routes remain the preferred methods for administering metronidazole in horses.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jvimsj\/aalaf032","type":"journal-article","created":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T09:02:25Z","timestamp":1768986145000},"source":"Crossref","is-referenced-by-count":0,"title":["Pharmacokinetic analysis and steady-state predictions of different preparations of metronidazole administered per rectum in adult horses"],"prefix":"10.1093","volume":"40","author":[{"given":"Jenni R E","family":"Auvinen","sequence":"first","affiliation":[{"name":"Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Purdue University , West Lafayette, IN 47907 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janice E","family":"Kritchevsky","sequence":"additional","affiliation":[{"name":"Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Purdue University , West Lafayette, IN 47907 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer M","family":"Reinhart","sequence":"additional","affiliation":[{"name":"Department of Veterinary Clinical Medicine, University of Illinois Urbana-Champaign , Urbana, IL 61802 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandria E","family":"Gochenauer","sequence":"additional","affiliation":[{"name":"Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Purdue University , West Lafayette, IN 47907 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amber S","family":"Jannasch","sequence":"additional","affiliation":[{"name":"Bindley Bioscience Center, Purdue University , West Lafayette, IN 47907 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Han-Hallett","sequence":"additional","affiliation":[{"name":"Bindley Bioscience Center, Purdue University , West Lafayette, IN 47907 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2026,1,21]]},"reference":[{"key":"2026020706121020400_ref1","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.2460\/javma.1991.198.06.1045","article-title":"Clinical use of metronidazole in horses: 200 cases (1984-1989)","volume":"198","author":"Sweeney","year":"1991","journal-title":"J Am Vet Med Assoc"},{"key":"2026020706121020400_ref2","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1111\/j.1365-2885.2004.00603.x","article-title":"Pharmacokinetic\/pharmacodynamic relationships of antimicrobial drugs used in veterinary medicine","volume":"27","author":"McKellar","year":"2004","journal-title":"J Vet Pharmacol 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