{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T13:52:34Z","timestamp":1775742754381,"version":"3.50.1"},"reference-count":38,"publisher":"American Veterinary Medical Association (AVMA)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ajvr"],"published-print":{"date-parts":[[2004,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n\t\t\t\t<jats:p>\n\t\t\t\t\t<jats:bold>Objective<\/jats:bold>\u2014To determine cyclooxygenase-2 (COX-2)\nselectivity, pharmacokinetic properties, and in vivo\nefficacy of ML-1,785,713 in dogs.<\/jats:p>\n\t\t\t\t<jats:p>\n\t\t\t\t\t<jats:bold>Animals<\/jats:bold>\u201421 healthy male and female mixed-breed\ndogs and 24 healthy male Beagles.<\/jats:p>\n\t\t\t\t<jats:p>\n\t\t\t\t\t<jats:bold>Procedure<\/jats:bold>\u2014Selectivity of ML-1,785,713 for inhibiting\nCOX-2 was determined by comparing the potency for\ninhibiting cyclooxygenase-1 (COX-1) with that of COX-2 in canine blood. Pharmacokinetic properties were\ndetermined after IV (2 mg\/kg) and oral (8 mg\/kg)\nadministration in female mixed-breed dogs. In vivo\nefficacy was evaluated in male mixed-breed dogs\nwith urate crystal-induced synovitis. Prophylactic efficacy\nwas evaluated by administering ML-1,785,713\ntwo hours before induction of synovitis whereas therapeutic\nefficacy was determined by administering\nML-1,785,713 one hour after induction of synovitis.<\/jats:p>\n\t\t\t\t<jats:p>\n\t\t\t\t\t<jats:bold>Results<\/jats:bold>\u2014Blood concentrations that resulted in 50%\ninhibition of COX-1 and COX-2 activity in vitro were\n119.1\u00b5M and 0.31\u00b5M, respectively, and selectivity\nratio for inhibiting COX-2 relative to COX-1 was 384.\nML-1,785,713 had high oral bioavailability (101%), low\nsystemic clearance (7.7 mL\/min\/kg), and an elimination\nhalf-life of 5.9 hours. ML-1,785,713 was efficacious\nwhen administered prophylactically and therapeutically\nto dogs with urate crystal-induced synovitis.<\/jats:p>\n\t\t\t\t<jats:p>\n\t\t\t\t\t<jats:bold>Conclusions and Clinical Relevance<\/jats:bold>\u2014ML-1,785,713\nis a novel, potent COX-2 inhibitor that is the most\nselective COX-2 inhibitor described for use in dogs to\ndate. ML-1,785,713 has oral bioavailability and low\nsystemic clearance that is comparable to other nonsteroidal\nanti-inflammatory drugs. It is effective after\nprophylactic and therapeutic administration in attenuating\nlameness in dogs with urate crystal-induced\nsynovitis. Drugs that specifically inhibit COX-2 and not\nCOX-1 at therapeutic doses may have an improved\ntolerability profile, compared with nonselective nonsteroidal\nanti-inflammatory drugs. 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