{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T17:13:00Z","timestamp":1692897180042},"reference-count":45,"publisher":"Wiley","issue":"S1","license":[{"start":{"date-parts":[[2022,7,5]],"date-time":"2022-07-05T00:00:00Z","timestamp":1656979200000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100012752","name":"Elanco Animal Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012752","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Vet Pharm &amp; Therapeutics"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Transdermal buprenorphine solution (TBS) is approved for the control of postoperative pain in cats where a single preoperative dose provides 4\u00a0days of analgesia. It is administered as a unit dose of 8\u00a0mg to cats weighing 1.2\u20133\u00a0kg and 20\u00a0mg to cats weighing to &gt;3\u20137.5\u00a0kg, which is equivalent to a dosage on a bodyweight basis of 2.7\u20136.7\u00a0mg\/kg. In this safety study, the 1X dose was defined as 6.7\u00a0mg\/kg. Thirty\u2010two cats (16\u00a0males and 16\u00a0females) were randomly allocated to placebo, 1, 2, and 3X TBS administered topically to the dorsal cervical skin every 4\u00a0days for 3 doses. Clinical observations, behavioral scores, mydriasis score (yes\/no), and physiological variables were assessed or measured prior to each dose administration (0\u00a0h) and at 1, 2, 4, 8, 12, 24, 36, 48, and 72\u00a0h following each treatment and prior to euthanasia on Day 12 or 13. Blood samples for clinical pathology were collected on Days \u2010 1, 4, 8, and prior to euthanasia. There was little evidence of respiratory, cardiovascular, or gastrointestinal effects. Respiratory rates were above the reference range in all groups and lower by 10\u00a0breaths\/min in the 3X group during the third dosing interval compared to placebo. There were no differences in heart rates. Constipation was transiently observed in approximately equal numbers in placebo\u2010 and TBS\u2010treated cats. Behavioral scores showed sedation or euphoria was transient in the first dosing interval but became more prolonged with each dosing interval. Mydriasis was prolonged in the first dosing interval and diminished by the third dosing interval consistent with accommodation. Mean body temperatures in TBS\u2010treated cats were up to 0.6\u00b0C (1.8\u00b0F) greater than placebo\u2010treated cats. There were no clinically relevant changes to serum chemistry, hematology, or urinalysis outcomes nor gross or microscopic observations attributable to TBS. These data demonstrate that TBS is safe and well\u2010tolerated when administered to 16\u2010week\u2010old cats at multiples of the approved dose and duration and supports clinical safety in the event of delayed buprenorphine metabolism, medication errors, or alterations in the dosing regimen.<\/jats:p>","DOI":"10.1111\/jvp.13051","type":"journal-article","created":{"date-parts":[[2022,7,5]],"date-time":"2022-07-05T12:51:09Z","timestamp":1657025469000},"update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Margin of safety of extended\u2010duration transdermal buprenorphine solution following multiple\u2010dose administrations to cats"],"prefix":"10.1111","volume":"45","author":[{"given":"Terrence P.","family":"Clark","sequence":"first","affiliation":[{"name":"Nexcyon Pharmaceuticals, Inc.  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Rockwood Tennessee USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kim M.","family":"Newkirk","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Biomedical and Diagnostic Sciences Department University of Tennessee  Knoxville Tennessee USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"Aulbach","sequence":"additional","affiliation":[{"name":"MPI Research, Inc.  Mattawan Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ting\u2010Li","family":"Lin","sequence":"additional","affiliation":[{"name":"Nexcyon Pharmaceuticals, Inc.  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