{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T19:26:04Z","timestamp":1766085964917,"version":"3.30.1"},"reference-count":33,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2008,7,7]],"date-time":"2008-07-07T00:00:00Z","timestamp":1215388800000},"content-version":"vor","delay-in-days":2712,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vet Pharm &amp; Therapeutics"],"published-print":{"date-parts":[[2001,2,2]]},"abstract":"<jats:p>The present experiment was designed to determine a dosage regimen (dose, interval of administration) in the dog for nimesulide, a nonsteroidal anti\u2010inflammatory drug with<jats:italic>in vitro<\/jats:italic>selectivity for the inhibition of cyclo\u2010oxygenase 2 (Cox\u20102), using a pharmacokinetic\/pharmacodynamic (PK\/PD) approach. The PK\/PD results were compared with those obtained using a classical dose titration study. In the PK\/PD experiment, 11 dogs were subjected to Freund\u2019s adjuvant arthritis characterized by permanent hyperthermia. Nimesulide (5\u2003mg\/kg, oral route) was tested during the secondary phase of the inflammatory response. In the dose titration study, nimesulide (0, 3, 6 and 9\u2003mg\/kg, oral route) was tested in eight other dogs using a reversible urate crystal arthritis in a 4\u2010period crossover design. Different PD endpoints (including lameness assessed by force plate and hyperthermia) were regularly measured during the PK\/PD experiment, and plasma samples were obtained to determine the plasma nimesulide concentration. The data were modeled using an indirect effect model. The<jats:italic>IC<\/jats:italic><jats:sub>50<\/jats:sub>of nimesulide for lameness was 6.26\u2003\u00b1\u20033.01\u2003\u03bcg\/mL, which was significantly higher than the<jats:italic>EC<\/jats:italic><jats:sub>50<\/jats:sub>value obtained for antipyretic effect (2.72\u2003\u00b1\u20031.29\u2003\u03bcg\/mL). The<jats:italic>ED<\/jats:italic><jats:sub>50<\/jats:sub>estimated from the classical dose titration study were 1.34\u2003mg\/kg (lameness) and 3.0\u2003mg\/kg (skin temperature). The PK\/PD parameters were used to simulate different dosage regimens (dose, interval of administration). The antipyretic and anti\u2010inflammatory effects were calculated from the model for the recommended dosage regimen (5\u2003mg\/kg\/24\u2003h). It was apparent from this approach, that this dosage regimen enabled 76% of the theoretical maximal drug efficacy to be obtained for pyresis and 43% for lameness. It was concluded from the comparison of<jats:italic>in vivo<\/jats:italic>and<jats:italic>in vitro IC<\/jats:italic><jats:sub>50<\/jats:sub>, that nimesulide is a potent NSAID for which some Cox\u20101 inhibition is required to obtain clinically relevant efficacy.<\/jats:p>","DOI":"10.1046\/j.1365-2885.2001.00304.x","type":"journal-article","created":{"date-parts":[[2003,3,12]],"date-time":"2003-03-12T09:22:48Z","timestamp":1047460968000},"page":"43-55","source":"Crossref","is-referenced-by-count":45,"title":["A pharmacokinetic\/pharmacodynamic approach vs. a dose titration for the determination of a dosage regimen: the case of nimesulide, a Cox\u20102 selective nonsteroidal anti\u2010inflammatory drug in the dog"],"prefix":"10.1111","volume":"24","author":[{"given":"P. L.","family":"Toutain","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. 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