{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:55:21Z","timestamp":1786978521376,"version":"build-2736575974"},"reference-count":17,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T00:00:00Z","timestamp":1638403200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Veterinary Medicine &amp; Sci"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Enflicoxib is a newly developed NSAID of the coxib class. The optimal therapeutic dose to be confirmed in the field studies was established using a combination of pharmacokinetic (PK) modelling and pharmacodynamic (PD) studies. First, a PK study was performed to determine the plasmatic profile of enflicoxib and its active pyrazol metabolite in dogs. Thereafter, two studies using a urate crystal\u2010induced acute arthritis model allowed to correlate efficacy with plasmatic concentrations. Finally, a population PK model was developed to establish the Minimum Effective Concentration (MEC) and the Maximum Tolerated Concentration (MTC). Enflicoxib plasma concentrations were highest for the first 48\u00a0h. Thereafter, pyrazol metabolite concentrations were higher and persisted up to the end of the study. No reduction on the lameness (CLS) or pain scores (PS) was observed in the first hours after enflicoxib administration so no MEC could be established for the parent compound. Both CLS and PS were greatly reduced when the pyrazol metabolite achieved concentrations of 411\u00a0ng\/ml or higher, so this concentration was established as the MEC for the pyrazol metabolite. Enflicoxib MTC was established at 6723\u00a0ng\/ml whereas for the pyrazol metabolite it was 4258\u00a0ng\/ml. The population PK model showed that a loading enflicoxib dose of 8\u00a0mg\/kg followed by weekly maintenance doses of 4\u00a0mg\/kg would achieve stable concentrations of the pyrazol metabolite within the therapeutic window (between the MEC and the MTC), and it was considered the most adequate posology to be confirmed in the field clinical studies for the treatment of canine osteoarthritis.<\/jats:p>","DOI":"10.1002\/vms3.670","type":"journal-article","created":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T03:53:12Z","timestamp":1638417192000},"page":"31-45","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Pharmacology of enflicoxib, a new coxib drug: Efficacy and dose determination by clinical and pharmacokinetic\u2010guided approach for the treatment of osteoarthritis in dogs based on an acute arthritis induction model"],"prefix":"10.1002","volume":"8","author":[{"given":"Josep\u2010Maria","family":"Cendr\u00f3s","sequence":"first","affiliation":[{"name":"Biopharmaceutics and Pharmacokinetics Unit, Faculty of Pharmacy and Food Sciences Department of Pharmacy and Pharmaceutical Technology and Physical Chemistry, University of Barcelona  Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Salichs","sequence":"additional","affiliation":[{"name":"Ecuphar Veterinaria SLU (Animalcare Group)  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregorio","family":"Encina","sequence":"additional","affiliation":[{"name":"Welab Barcelona Barcelona Science Park (PCB)  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose Miguel","family":"Vela","sequence":"additional","affiliation":[{"name":"Welab Barcelona Barcelona Science Park (PCB)  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5440-7699","authenticated-orcid":false,"given":"Josep M.","family":"Homedes","sequence":"additional","affiliation":[{"name":"Ecuphar Veterinaria SLU (Animalcare Group)  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,12,2]]},"reference":[{"key":"e_1_2_10_2_1","volume-title":"NONMEM user's guide","author":"Beal S.","year":"2009"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.2460\/ajvr.2003.64.1429"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.2147\/JPR.S75160"},{"issue":"1","key":"e_1_2_10_5_1","first-page":"10","article-title":"Assessment of the efficacy of firocoxib and robenacoxib in an induced synovitis model of acute arthritis in dogs","volume":"15","author":"Dauteloup C.","year":"2017","journal-title":"International Journal of Applied Research in Veterinary Medicine"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12917\u2010019\u20102052\u20100"},{"key":"e_1_2_10_7_1","unstructured":"European Medicines Agency. 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