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Firstly, the effect of different ketoprofen doses as mono\u2010substance (1, 3, and 6\u00a0mg\/kg subcutaneous) on lipopolysaccharide\u2010induced fever was evaluated which indicated that rectal temperature reduction lasted longer in the calves receiving 3 and 6\u00a0mg\/kg ketoprofen. Secondly, the PK profile of the combination product was compared with mono\u2010substance products (3\u00a0mg\/kg subcutaneous and intramuscular). The PK profile of ketoprofen in the combination product was characterized by longer<jats:italic>t<\/jats:italic><jats:sub>1\/2<\/jats:sub>, lower<jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>and increased AUC in comparison with mono\u2010substance products. Due to prolonged ketoprofen exposure in the combination product, the pyrexia reducing effect of the combination product lasted longer in a second lipopolysaccharide challenge study in comparison with mono\u2010substance products. Finally, a PK\u2010PD model for the anti\u2010pyretic effect of ketoprofen was developed based on the data from the different studies. The PK\u2010PD model eliminated the need for additional animal experiments and indicated that a 3\u00a0mg\/kg ketoprofen dose in the combination product provided optimal efficacy.<\/jats:p>","DOI":"10.1111\/jvp.12999","type":"journal-article","created":{"date-parts":[[2021,8,13]],"date-time":"2021-08-13T11:44:05Z","timestamp":1628855045000},"page":"69-82","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Co\u2010formulation of ketoprofen with tulathromycin alters pharmacokinetic and pharmacodynamic profile of ketoprofen in cattle"],"prefix":"10.1111","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2891-0298","authenticated-orcid":false,"given":"Jenne","family":"De Koster","sequence":"first","affiliation":[{"name":"Zoetis Veterinary Medicine Research and Development Zaventem Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph F.","family":"Boucher","sequence":"additional","affiliation":[{"name":"Zoetis Veterinary Medicine Research and Development Kalamazoo MI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jezaniah\u2010Kira","family":"Tena","sequence":"additional","affiliation":[{"name":"Zoetis Veterinary Medicine Research and Development Kalamazoo MI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1329-201X","authenticated-orcid":false,"given":"Ronette","family":"Gehring","sequence":"additional","affiliation":[{"name":"Division of Veterinary and Comparative Pharmacology Faculty of Veterinary Medicine Institute for Risk Assessment Sciences Utrecht University Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael R.","family":"Stegemann","sequence":"additional","affiliation":[{"name":"Zoetis Veterinary Medicine Research and Development Zaventem Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,8,13]]},"reference":[{"key":"e_1_2_10_2_1","volume-title":"The physiological basis of veterinary clinical pharmacology","author":"Baggot J. 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