{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T22:34:42Z","timestamp":1792708482249,"version":"4.5.0"},"reference-count":34,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2014,10,10]],"date-time":"2014-10-10T00:00:00Z","timestamp":1412899200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Lab Anim"],"published-print":{"date-parts":[[2015,4]]},"abstract":"<jats:p>The use of appropriate analgesia in laboratory mice may be suboptimal because of concerns about adverse events (AE). Target Animal Safety trials were conducted to determine the safety of an extended-release suspension of buprenorphine. Drug or control suspensions were injected subcutaneously in surgically-treated BALB\/c mice anesthetized with ketamine\u2013xylazine to mimic post-operative conditions in which the compound might commonly be administered. Single and repeat five-fold (5\u00d7) excesses of the 3.25\u2009mg\/kg intended dose were used to provoke potential AE. Trials included prospective measurements of weight changes, blood chemistry, hematology, and histopathology. Clinical and histopathology findings were similar in drug-treated and control mice in a four-day trial using a single 16.25\u2009mg\/kg, 5\u00d7 overdose of the drug. In a 12-day trial, which used a total buprenorphine dose of 48.75\u2009mg\/kg, clinical and histopathology values were also similar in control and drug-treated female mice. In the male arm of the repeat-overdose trial, two of eight mice died on the morning of day 12, three days following the third 16.25\u2009mg\/kg overdose administration. Histopathology did not reveal a cause of death. In a 14-month trial using a single 3.25\u2009mg\/kg dose of the drug, no significant findings identified potential AE. These findings indicate a high tolerance to an extended-release buprenorphine suspension administered post-operatively in mice with appropriate husbandry.<\/jats:p>","DOI":"10.1177\/0023677214554216","type":"journal-article","created":{"date-parts":[[2014,10,11]],"date-time":"2014-10-11T01:08:35Z","timestamp":1412989715000},"page":"100-110","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":13,"title":["Safety studies of post-surgical buprenorphine therapy for mice"],"prefix":"10.1177","volume":"49","author":[{"given":"Karl A","family":"Traul","sequence":"first","affiliation":[{"name":"Pharmaceutical Consulting, Lawrenceville, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennell B","family":"Romero","sequence":"additional","affiliation":[{"name":"Johns Hopkins School of Medicine, Department of Molecular and Comparative Pathobiology, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cory","family":"Brayton","sequence":"additional","affiliation":[{"name":"Johns Hopkins School of Medicine, Department of Molecular and Comparative Pathobiology, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis","family":"DeTolla","sequence":"additional","affiliation":[{"name":"University of Maryland, School of Medicine, Departments of Pathology, Medicine, Division of Infectious Diseases and Public Health, and the Program of Comparative Medicine, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Forbes-McBean","sequence":"additional","affiliation":[{"name":"Johns Hopkins School of Medicine, Department of Molecular and Comparative Pathobiology, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew S","family":"Halquist","sequence":"additional","affiliation":[{"name":"Virginia Commonwealth University School of Pharmacy, Department of Pharmaceutics, Richmond, VA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H Thomas","family":"Karnes","sequence":"additional","affiliation":[{"name":"Virginia Commonwealth University School of Pharmacy, Department of Pharmaceutics, Richmond, VA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Sarabia-Estrada","sequence":"additional","affiliation":[{"name":"Johns Hopkins School of Medicine, Department of Neurological Surgery, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J","family":"Tomlinson","sequence":"additional","affiliation":[{"name":"Nova Pathology, Bellingham, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betty M","family":"Tyler","sequence":"additional","affiliation":[{"name":"Johns Hopkins School of Medicine, Department of Neurological Surgery, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobu","family":"Ye","sequence":"additional","affiliation":[{"name":"Johns Hopkins School of Medicine, Department of Neurological Surgery, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Zadnik","sequence":"additional","affiliation":[{"name":"Johns Hopkins School of Medicine, Department of Neurological Surgery, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Guarnieri","sequence":"additional","affiliation":[{"name":"Johns Hopkins School of Medicine, Department of Neurological Surgery, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2014,10,10]]},"reference":[{"key":"bibr1-0023677214554216","doi-asserted-by":"publisher","DOI":"10.1258\/la.2008.008020"},{"key":"bibr2-0023677214554216","first-page":"8","volume":"39","author":"Gades NM","year":"2000","journal-title":"Contemp Top Lab Anim Sci"},{"key":"bibr3-0023677214554216","doi-asserted-by":"publisher","DOI":"10.1258\/la.2012.012058"},{"key":"bibr4-0023677214554216","doi-asserted-by":"publisher","DOI":"10.1258\/0023677011911651"},{"key":"bibr5-0023677214554216","doi-asserted-by":"publisher","DOI":"10.1258\/002367700780457509"},{"key":"bibr6-0023677214554216","first-page":"558","volume":"54","author":"Clark MD","year":"2002","journal-title":"Comp Med"},{"key":"bibr7-0023677214554216","doi-asserted-by":"publisher","DOI":"10.1213\/00000539-199410000-00015"},{"key":"bibr8-0023677214554216","doi-asserted-by":"publisher","DOI":"10.1258\/la.2009.009029"},{"key":"bibr9-0023677214554216","doi-asserted-by":"publisher","DOI":"10.1016\/j.tvjl.2009.11.013"},{"key":"bibr10-0023677214554216","first-page":"293","volume":"54","author":"Thompson AC","year":"2004","journal-title":"Comp Med"},{"key":"bibr11-0023677214554216","first-page":"300","volume":"47","author":"Clark JA","year":"1997","journal-title":"Lab Anim Sci"},{"key":"bibr12-0023677214554216","doi-asserted-by":"publisher","DOI":"10.1258\/002367702320162423"},{"key":"bibr13-0023677214554216","doi-asserted-by":"publisher","DOI":"10.1097\/ADM.0b013e31806c9202"},{"key":"bibr14-0023677214554216","doi-asserted-by":"publisher","DOI":"10.1038\/laban.152"},{"key":"bibr15-0023677214554216","unstructured":"Guidance for Industry (GFI#61) \u2013 FDA Approval of Animal Drugs for Minor Uses and for Minor Species. Target animal safety and effectiveness protocol development and submission. www.fda.gov\/downloads\/AnimalVeterinary\/GuidanceComplianceEnforcement\/guidanceforindustry\/ucm052375.pdf, (accessed October 2014)."},{"key":"bibr16-0023677214554216","unstructured":"Guidelines of Target Animal Safety for Pharmaceuticals, November VICH Topic GL43, European Medicines Agency Veterinary Medicines and Inspections. 2006."},{"key":"bibr17-0023677214554216","unstructured":"Guidance for Industry 185.\n                      Target animal safety for veterinary pharmaceutical products.\n                      VICH GL43. US Department of Health and Human Services Food and Drug Administration Center for Veterinary Medicine, 24 April 2009."},{"key":"bibr18-0023677214554216","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-007-9470-6"},{"key":"bibr19-0023677214554216","doi-asserted-by":"publisher","DOI":"10.1016\/j.tvjl.2010.01.013"},{"key":"bibr20-0023677214554216","doi-asserted-by":"publisher","DOI":"10.1111\/j.1360-0443.2006.01348.x"},{"key":"bibr21-0023677214554216","unstructured":"Alzet Osmotic Pump Implantation. www.alzet.com\/resources\/index."},{"key":"bibr22-0023677214554216","unstructured":"Johns Hopkins Medicine. www.hopkinsmedicine.org\/mcp\/PHENOCORE\/."},{"key":"bibr23-0023677214554216","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-381361-9.00002-0"},{"key":"bibr24-0023677214554216","doi-asserted-by":"publisher","DOI":"10.1354\/vp.38-1-1"},{"key":"bibr25-0023677214554216","doi-asserted-by":"publisher","DOI":"10.4103\/0975-7406.124316"},{"key":"bibr26-0023677214554216","first-page":"157","volume":"45","author":"Banerjee D","year":"1997","journal-title":"Folia Biol (Krakow)"},{"key":"bibr27-0023677214554216","doi-asserted-by":"publisher","DOI":"10.1258\/002367799780578183"},{"key":"bibr28-0023677214554216","first-page":"11","volume":"47","author":"Buitrago S","year":"2008","journal-title":"J Am Assoc Lab Anim Sci"},{"key":"bibr29-0023677214554216","first-page":"487","volume":"56","author":"Smith LJ","year":"2006","journal-title":"Comp Med"},{"key":"bibr30-0023677214554216","first-page":"507","volume":"50","author":"Schmidt JR","year":"2011","journal-title":"J Am Assoc Lab Anim Sci"},{"key":"bibr31-0023677214554216","first-page":"60","volume":"59","author":"Curtin LI","year":"2009","journal-title":"Comp Med"},{"key":"bibr32-0023677214554216","first-page":"448","volume":"51","author":"Kolstad AM","year":"2012","journal-title":"J Am Assoc Lab Anim Sci"},{"key":"bibr33-0023677214554216","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2009.04.003"},{"key":"bibr34-0023677214554216","first-page":"192","volume":"50","author":"McKeon GP","year":"2011","journal-title":"J Am Assoc Lab Anim Sci"}],"container-title":["Laboratory Animals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0023677214554216","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/0023677214554216","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0023677214554216","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T07:34:25Z","timestamp":1777620865000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/0023677214554216"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,10,10]]},"references-count":34,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2015,4]]}},"alternative-id":["10.1177\/0023677214554216"],"URL":"https:\/\/doi.org\/10.1177\/0023677214554216","relation":{},"ISSN":["0023-6772","1758-1117"],"issn-type":[{"value":"0023-6772","type":"print"},{"value":"1758-1117","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,10,10]]}}}