{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:14:49Z","timestamp":1787015689327,"version":"build-2736575974"},"reference-count":18,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000},"content-version":"vor","delay-in-days":171,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,8,30]],"date-time":"2025-08-30T00:00:00Z","timestamp":1756512000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013678","name":"Cancer Center, University of Colorado","doi-asserted-by":"publisher","award":["P30CA46934"],"award-info":[{"award-number":["P30CA46934"]}],"id":[{"id":"10.13039\/100013678","id-type":"DOI","asserted-by":"publisher"}]},{"name":"College Research Council, Colorado State University College of Veterinary Medicine and Biomedical Sciences"},{"DOI":"10.13039\/100013678","name":"Cancer Center, University of Colorado","doi-asserted-by":"publisher","award":["P30CA46934"],"award-info":[{"award-number":["P30CA46934"]}],"id":[{"id":"10.13039\/100013678","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Grape-induced acute kidney injury (AKI) is caused by tartaric acid and may lead to death in dogs. Probenecid, an organic anion transporter-1 inhibitor, recently has been shown to block the uptake of tartaric acid in Madin\u2013Darby canine kidney cells and has been suggested as a possible target for prevention of AKI after grape ingestion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Hypothesis\/Aims<\/jats:title>\n                    <jats:p>Assess the safety and pharmacokinetics (PK) of PO probenecid in dogs. We hypothesized that probenecid would result in mild, self-limiting gastrointestinal (GI) adverse effects and would be safe in healthy dogs. Additionally, we hypothesized that PO probenecid (50\u2009mg\/kg) would have adequate bioavailability and achieve pharmacologically active plasma drug concentrations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Animals<\/jats:title>\n                    <jats:p>Six healthy beagle dogs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Pharmacokinetic (PK) study. Dogs were given 50\u2009mg\/kg of probenecid PO, with PK data collected for 48\u2009h after administration. Complete blood count, serum biochemistry profile, urinalysis, and clinical monitoring were performed throughout a 21-day study period to assess safety. Plasma concentration versus time data was analyzed using non-compartmental and two-compartmental modeling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Orally administered probenecid had excellent estimated bioavailability (82.6%) and rapid absorption, with a mean maximal plasma concentration of 589.3\u2009\u03bcM (range: 368.0\u2013830.5\u2009\u03bcM) within 1.5\u2009h. The mean volume of distribution was 0.71\u2009L\/kg, with mean systemic clearance of 0.022\u2009L\/h\/kg and mean half-life of 24.1\u2009h. Probenecid was well tolerated by all six dogs, with no clinically relevant adverse effects noted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Clinical Importance<\/jats:title>\n                    <jats:p>Orally administered probenecid is safe and bioavailable in healthy dogs. Future clinical trials assessing PO probenecid in dogs with known tartaric acid ingestion are warranted.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jvim.70221","type":"journal-article","created":{"date-parts":[[2025,8,30]],"date-time":"2025-08-30T14:34:53Z","timestamp":1756564493000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Evaluation of the Safety and Pharmacokinetics of Single-Dose Oral Probenecid Administration in\u00a0Healthy Dogs"],"prefix":"10.1093","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1141-3236","authenticated-orcid":false,"given":"Margaret","family":"Cook","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine and Biomedical Sciences, Colorado State University Department of Clinical Sciences, , Fort Collins, Colorado,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel L.","family":"Gustafson","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine and Biomedical Sciences, Colorado State University Department of Clinical Sciences, , Fort Collins, Colorado,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie","family":"Kroeker","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine and Biomedical Sciences, Colorado State University Department of Clinical Sciences, , Fort Collins, Colorado,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Shropshire","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine and Biomedical Sciences, Colorado State University Department of Clinical Sciences, , Fort Collins, Colorado,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin M.","family":"Zersen","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine and Biomedical Sciences, Colorado State University Department of Clinical Sciences, , Fort Collins, Colorado,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,9,1]]},"reference":[{"issue":"5","key":"2026022003565602800_jvim70221-bib-0001","first-page":"1555","article-title":"Renal Failure Associated With Ingestion of Grapes or Raisins in Dogs","volume":"218","author":"Gwaltney-Brant","year":"2001","journal-title":"Journal of the American Veterinary Medical Association"},{"key":"2026022003565602800_jvim70221-bib-0002","first-page":"485","volume-title":"Blackwell's Five-Minute\u00a0Veterinary Consult Small Animal Toxicology","author":"Hoffber","year":"2016","edition":"2nd ed."},{"issue":"5","key":"2026022003565602800_jvim70221-bib-0003","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1111\/vec.12905","article-title":"Retrospective Evaluation of the Clinical Course and Outcome Following Grape or Raisin 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