{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T16:36:57Z","timestamp":1790267817046,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T00:00:00Z","timestamp":1763510400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T00:00:00Z","timestamp":1763510400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Vet Pharm &amp; Therapeutics"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>P\u2010glycoprotein (P\u2010gp) greatly impacts substrate drug disposition, so much so that regulatory agencies recommend ascertaining the P\u2010gp status of active pharmaceutical ingredients (APIs) intended for human use. Arguably, the P\u2010gp status of drugs intended for canine patients is equally, if not more, important. Our research objectives were to assess whether human P\u2010gp substrate data can predict canine P\u2010gp substrate status and to explore the three previously reported binding sites within the P\u2010gp binding pocket, the H\u2010, R\u2010, and P\u2010sites. Competitive efflux assays employing cell lines expressing canine or human P\u2010gp were used to compare the degree of overlap or independence of the three binding sites in canine versus human P\u2010gp using site\u2010specific fluorescent P\u2010gp substrates rhodamine 123, calcein AM and Hoechst 33342. Because calcein AM can also be transported by multidrug resistance protein 1 (MRP1), experiments were performed to assess its potential influence on calcein AM efflux studies. Results indicate that: (i) MRP1 is either a non\u2010factor or negligible factor for cells expressing canine or human P\u2010gp respectively; (ii) determining an API's P\u2010gp binding site may provide clinically relevant information; and (iii) use of human P\u2010gp substrate data as a proxy for canine P\u2010gp substrate data will often prove inaccurate.<\/jats:p>","DOI":"10.1111\/jvp.70034","type":"journal-article","created":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T08:37:01Z","timestamp":1763541421000},"page":"120-130","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Comparison of Human and Canine P\u2010Glycoprotein Substrates at R, P, and H Binding Sites"],"prefix":"10.1111","volume":"49","author":[{"given":"Neal S.","family":"Burke","sequence":"first","affiliation":[{"name":"Program in Individualized Medicine (PrIMe), College of Veterinary Medicine Washington State University  Pullman Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1614-2903","authenticated-orcid":false,"given":"Katrina L.","family":"Mealey","sequence":"additional","affiliation":[{"name":"Program in Individualized Medicine (PrIMe), College of Veterinary Medicine Washington State University  Pullman Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,19]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4615-4811-9_6"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1917344"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/jsap.12618"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.acr.2014.10.003"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R114.609248"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvim.13827"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102567.2005.02116.x"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0928-0987(00)00117-2"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2004.08.026"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.01.041"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xphs.2017.04.018"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.20686"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dmpk.2021.100426"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.15.3.571"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2004.10.012"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20060715"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.5326\/JAAHA-MS-7004"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/00008571\u2010200"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvp.13123"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvp.12390"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1939-1676.2008.0122.x"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvim.12525"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvp.13102"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201200491"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2004.03.005"},{"issue":"1","key":"e_1_2_9_27_1","first-page":"149","article-title":"Flow Cytometric Assessment of P\u2010Glycoprotein and Multidrug Resistance\u2010Associated Protein Activity and Expression in Canine Lymphoma","volume":"29","author":"Po\u017aniak B.","year":"2015","journal-title":"In Vivo"},{"issue":"3","key":"e_1_2_9_28_1","first-page":"629","article-title":"Drug\u2013Drug Interaction Studies: Regulatory Guidance and an Industry Perspective","volume":"15","author":"Prueksaritanont T.","year":"2013","journal-title":"American Association of Pharmaceutical Scientists Journal"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1327.1999.00098.x"},{"key":"e_1_2_9_30_1","first-page":"227","article-title":"The Mechanism of ATP\u2010Dependent Multidrug Transport by P\u2010Glycoprotein","volume":"643","author":"Shapiro A. 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