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The objective of this work was to assess the mechanistic basis of enflicoxib therapy investigating the COX inhibitory activity of enflicoxib (racemate), its enantiomers and its main metabolites using the canine whole blood assay. The (R)\u2010(+)\u2010Enflicoxib enantiomer and metabolite M8 (hydroxylated pyrazoline) did not induce significant COX inhibition. Enflicoxib and its (S)\u2010(\u2010)\u2010Enflicoxib enantiomer inhibited COX\u20101 and COX\u20102 with variable degree of preferential isoform inhibition, but no significant therapeutic effect is anticipated in vivo. The pyrazol metabolite showed the highest COX\u20102 inhibition and was the most selective (IC<jats:sub>50<\/jats:sub> COX\u20101\/ COX\u20102 ratio: 19.45). As the pyrazol metabolite shows saturable binding to red blood cells, its in vivo concentrations in plasma are lower than in whole blood. Accordingly, when applying the red blood cell partitioning, the respective IC<jats:sub>50<\/jats:sub> and IC<jats:sub>80<\/jats:sub> for COX\u20102 inhibition decreased from 2.8\u00a0\u00b5M (1129\u00a0ng\/ml) and 13.4\u00a0\u00b5M (5404\u00a0ng\/ml) to 0.2\u00a0\u00b5M (80.7\u00a0ng\/ml) and 1.2\u00a0\u00b5M (484\u00a0ng\/ml) and the selectivity ratio increased to close to 55. The corrected pyrazol metabolite IC<jats:sub>50<\/jats:sub> and IC<jats:sub>80<\/jats:sub> are well within the plasma levels described in treated dogs.<\/jats:p>","DOI":"10.1111\/jvp.13042","type":"journal-article","created":{"date-parts":[[2022,1,17]],"date-time":"2022-01-17T16:08:04Z","timestamp":1642435684000},"page":"235-244","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Selective inhibition of cyclooxygenase\u20102 by enflicoxib, its enantiomers and its main metabolites in vitro in canine blood"],"prefix":"10.1111","volume":"45","author":[{"given":"Josep","family":"Sol\u00e0","sequence":"first","affiliation":[{"name":"Barcelona Science Park Experimental Toxicology and Ecotoxicology Unit (CERETOX)  Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00c0ngel","family":"Menargues","sequence":"additional","affiliation":[{"name":"Barcelona Science Park Experimental Toxicology and Ecotoxicology Unit (CERETOX)  Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5440-7699","authenticated-orcid":false,"given":"Josep","family":"Homedes","sequence":"additional","affiliation":[{"name":"Ecuphar veterinaria SLU (Animalcare Group)  Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Salichs","sequence":"additional","affiliation":[{"name":"Ecuphar veterinaria SLU (Animalcare Group)  Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"In\u00e9s","family":"\u00c1lvarez","sequence":"additional","affiliation":[{"name":"Welab Barcelona Science Park (PCB), Edifici Cl\u00faster II  Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luz","family":"Romero","sequence":"additional","affiliation":[{"name":"Welab Barcelona Science Park (PCB), Edifici Cl\u00faster II  Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Miguel","family":"Vela","sequence":"additional","affiliation":[{"name":"Welab Barcelona Science Park (PCB), Edifici Cl\u00faster II  Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,1,17]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0049\u20103848(85)90027\u20101"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1892\/0891\u20106640(2005)19[633:tcnpca]2.0.co;2"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02265118"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.2460\/ajvr.2001.62.1755"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/elps.200390182"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/vms3.670"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm0607247"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biochem.9b00659"},{"key":"e_1_2_10_10_1","unstructured":"European Commission(2021).Union Register of veterinary medicinal products.https:\/\/ec.europa.eu\/health\/documents\/community\u2010register\/html\/v270.htm"},{"key":"e_1_2_10_11_1","unstructured":"European Medicines Agency Committee for Medicinal Products for Human Use (CHMP)(effective date 01 Feb 2012).EMEA\/CHMP\/EWP\/192217\/2009 Rev. 1 Corr. 2**. 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