{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T08:26:07Z","timestamp":1786955167093,"version":"build-2736575974"},"reference-count":61,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T00:00:00Z","timestamp":1786752000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"QX001","award":["202405510510153"],"award-info":[{"award-number":["202405510510153"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background: The Biopharmaceutics Classification System (BCS) classifies drug substances according to their aqueous solubility and intestinal permeability; however, its application to veterinary drugs should account for species-specific gastrointestinal physiology. Grapiprant is a selective prostaglandin E2 receptor subtype 4 (EP4) antagonist approved as an oral tablet to control pain and inflammation associated with osteoarthritis in dogs, but its properties within the BCS framework remain unclear. Methods: This study evaluated the equilibrium solubility of grapiprant across pH conditions relevant to the canine gastrointestinal tract and calculated the dose number (D0) based on different gastric fluid volumes. A Caco-2 cell monolayer model was used to assess grapiprant intestinal permeability and the effects of time, concentration, pH, and efflux transporter inhibitors on its transepithelial transport. Results: Grapiprant showed relatively small changes in solubility across the tested pH range. D0 varied with pH and gastric fluid volume and approached or fell below 1 at larger fluid volumes. In the Caco-2 model, grapiprant showed generally limited apparent absorptive permeability, with permeability varying with pH. Efflux ratios were greater than 1, and verapamil reduced the efflux ratio, suggesting possible P-glycoprotein (P-gp) involvement. Conclusions: These findings suggest that both solubility and apparent intestinal permeability may limit the oral absorption of grapiprant under certain canine-relevant conditions. Accordingly, this study provides a biopharmaceutical characterization of grapiprant within the BCS framework rather than a definitive canine BCS classification, highlighting the importance of considering canine gastrointestinal conditions when interpreting its solubility and permeability. The results may support future optimization of dosing conditions and oral formulations.<\/jats:p>","DOI":"10.3390\/pharmaceutics18081010","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T08:05:41Z","timestamp":1786953941000},"page":"1010","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Biopharmaceutical Characterization of Grapiprant Within the BCS Framework Under Canine-Relevant Conditions: Solubility and Caco-2 Permeability Assessment"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-1122-3311","authenticated-orcid":false,"given":"Zeyu","family":"Wen","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"},{"name":"National Center for Veterinary Drug Safety Evaluation GCP Laboratory, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xilu","family":"Sun","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"},{"name":"National Center for Veterinary Drug Safety Evaluation GCP Laboratory, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumeng","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"},{"name":"National Center for Veterinary Drug Safety Evaluation GCP Laboratory, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyan","family":"Meng","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"},{"name":"National Center for Veterinary Drug Safety Evaluation GCP Laboratory, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runlin","family":"Yu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"},{"name":"National Center for Veterinary Drug Safety Evaluation GCP Laboratory, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyan","family":"Guo","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"},{"name":"National Center for Veterinary Drug Safety Evaluation GCP Laboratory, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2063-6260","authenticated-orcid":false,"given":"Xingyuan","family":"Cao","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"},{"name":"National Center for Veterinary Drug Safety Evaluation GCP Laboratory, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Piemontese, C., Girelli, C.R., Stabile, M., Lacitignola, L., Fraccascia, A., Crovace, A., Fanizzi, F.P., and Staffieri, F. 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