{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T04:08:23Z","timestamp":1746158903543,"version":"3.40.4"},"reference-count":28,"publisher":"American Veterinary Medical Association (AVMA)","issue":"5","license":[{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ajvr"],"published-print":{"date-parts":[[2025,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n<jats:sec id=\"sc_a1\">\n<jats:title>Objective<\/jats:title>\n<jats:p>To determine the pharmacokinetics of a single dose of flunixin transdermal formulation in American bullfrogs (<jats:italic>Lithobates catesbeianus<\/jats:italic>).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sc_a2\">\n<jats:title>Methods<\/jats:title>\n<jats:p>Clinically healthy, purpose-bred adult bullfrogs housed at the North Carolina State University College of Veterinary Medicine were enrolled in a sparse-sampling population study. Frogs were administered 3.3 mg\/kg transdermal flunixin meglumine (Banamine Transdermal; Merck Animal Health) on the dorsum via micropipette under manual restraint in July of 2022. Frogs were maintained in individual containers out of water for 4 hours and randomly assigned to 2 of the following venipuncture time points: 1, 2, 4, 8, 12, or 24 hours, with 7 frogs sampled per time point. Blood was collected from the popliteal sinus. Ultra performance liquid chromatography\u2013tandem mass spectrometry was used to determine plasma flunixin concentrations. Data were analyzed using noncompartmental analysis.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sc_a3\">\n<jats:title>Results<\/jats:title>\n<jats:p>Flunixin was detected in all samples collected from 21 bullfrogs (9 males and 12 females). A mean peak plasma concentration of 2.39 \u00b5g\/mL was reached between 1 and 2 hours. The elimination half-life was 15.0 hours. Plasma concentrations were similar across individuals at 1, 2, and 4 hours (range at 1 and 2 hours, 2.32 to 2.55 \u00b5g\/mL) but were variable at 8, 12, and 24 hours (range at 24 hours, 0.16 to 1.79 \u00b5g\/mL). Mucus and\/or epithelial loss was noted at the drug application site in 18 of 21 frogs. No additional clinical signs or mortality occurred.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sc_a4\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Transdermal flunixin was systemically absorbed, and plasma concentrations exceeded established therapeutic ranges in other species. Most frogs developed mild cutaneous lesions.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sc_a5\">\n<jats:title>Clinical Relevance<\/jats:title>\n<jats:p>Transdermal flunixin was detected in plasma for 24 hours; however, variability in plasma concentrations over time and topical side effects may limit its use.<\/jats:p>\n<\/jats:sec>","DOI":"10.2460\/ajvr.24.12.0414","type":"journal-article","created":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T14:47:17Z","timestamp":1741618037000},"source":"Crossref","is-referenced-by-count":0,"title":["Pharmacokinetics of a single dose of flunixin transdermal formulation in American bullfrogs (Lithobates catesbeianus)"],"prefix":"10.2460","volume":"86","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4569-0896","authenticated-orcid":true,"given":"Ashlyn C.","family":"Heniff","sequence":"first","affiliation":[{"name":"Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9834-2089","authenticated-orcid":true,"given":"Danielle A.","family":"Mzyk","sequence":"additional","affiliation":[{"name":"Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claire B.","family":"Giles","sequence":"additional","affiliation":[{"name":"Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3958-3912","authenticated-orcid":true,"given":"Larry J.","family":"Minter","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC"},{"name":"North Carolina Zoo, Asheboro, NC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7920-9338","authenticated-orcid":true,"given":"Ronald E.","family":"Baynes","sequence":"additional","affiliation":[{"name":"Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3667-0623","authenticated-orcid":true,"given":"Julie A.","family":"Balko","sequence":"additional","affiliation":[{"name":"Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1272","reference":[{"key":"B1","series-title":"Papich Handbook of Veterinary Drugs","first-page":"380","author":"Papich MG","year":"2020","unstructured":"Papich MG. Papich Handbook of Veterinary Drugs. 5th ed. Elsevier Health Sciences; 2020:380\u2013384."},{"issue":"4","key":"B2","series-title":"J Zoo Wildl Med","first-page":"680","article-title":"Effects of intramuscular meloxicam administration on prostaglandin E2 synthesis in the North American bullfrog (Rana catesbeiana)","volume":"42","author":"Minter LJ","year":"2011","unstructured":"Minter LJ, Clarke EO, Gjeltema JL, Archibald KE, Posner LP, Lewbart GA. Effects of intramuscular meloxicam administration on prostaglandin E2 synthesis in the North American bullfrog (Rana catesbeiana). J Zoo Wildl Med. 2011;42(4):680\u2013685. doi:10.1638\/2011-0126.1"},{"issue":"3","key":"B3","series-title":"Environ Toxicol Pharmacol","first-page":"373","article-title":"Vehicle effects on in vitro transdermal absorption of sevoflurane in the bullfrog, Rana catesbeiana","volume":"25","author":"Ardente AJ","year":"2008","unstructured":"Ardente AJ, Barlow BM, Burns P, Goldman R, Baynes RE. Vehicle effects on in vitro transdermal absorption of sevoflurane in the bullfrog, Rana catesbeiana. Environ Toxicol Pharmacol. 2008;25(3):373\u2013379. doi:10.1016\/j.etap.2007.12.001"},{"issue":"1","key":"B4","series-title":"J Exot Pet Med","first-page":"50","article-title":"Advances in amphibian clinical therapeutics","volume":"23","author":"Chinnadurai SK","year":"2014","unstructured":"Chinnadurai SK, Kane LP. Advances in amphibian clinical therapeutics. J Exot Pet Med. 2014;23(1):50\u201355. doi:10.1053\/j.jepm.2013.11.008"},{"issue":"1","key":"B5","series-title":"J Zoo Wildl Med","first-page":"51","article-title":"Plasma pharmacokinetics of selamectin after a single topical administration in the American bullfrog (Rana catesbeiana)","volume":"38","author":"D\u2019Agostino JJ","year":"2007","unstructured":"D\u2019Agostino JJ, West G, Boothe DM, Jayanna PK, Snider T, Hoover JP. Plasma pharmacokinetics of selamectin after a single topical administration in the American bullfrog (Rana catesbeiana). J Zoo Wildl Med. 2007;38(1):51\u201354. doi:10.1638\/06-054.1"},{"issue":"2","key":"B6","series-title":"J Vet Pharmacol Ther","first-page":"109","article-title":"Percutaneous absorption of chemicals: developing an understanding for the treatment of disease in frogs","volume":"39","author":"Llewelyn VK","year":"2016","unstructured":"Llewelyn VK, Berger L, Glass BD. Percutaneous absorption of chemicals: developing an understanding for the treatment of disease in frogs. J Vet Pharmacol Ther. 2016;39(2):109\u2013121. doi:10.1111\/jvp.12264"},{"issue":"2","key":"B7","series-title":"J Zoo Wildl Med","first-page":"344","article-title":"The pharmacokinetics of topical itraconazole in Panamanian golden frogs (Atelopus zeteki)","volume":"48","author":"Rifkin A","year":"2017","unstructured":"Rifkin A, Visser M, Barrett K, Boothe D, Bronson E. The pharmacokinetics of topical itraconazole in Panamanian golden frogs (Atelopus zeteki). J Zoo Wildl Med. 2017;48(2):344\u2013351. doi:10.1638\/2015-0218R2.1"},{"issue":"3\u20134","key":"B8","series-title":"J Herpetol Med Surg","first-page":"89","article-title":"Plasma concentrations of ketoprofen and meloxicam after subcutaneous and topical administration in the smoky jungle frog (Leptodactylus pentadactylus)","volume":"28","author":"Balko JA","year":"2018","unstructured":"Balko JA, Watson MK, Papich MG, Posner LP, Chinnadurai SK. Plasma concentrations of ketoprofen and meloxicam after subcutaneous and topical administration in the smoky jungle frog (Leptodactylus pentadactylus). J Herpetol Med Surg. 2018;28(3\u20134):89\u201392. doi:10.5818\/17-10-129.1"},{"issue":"2","key":"B9","series-title":"J Herpetol Med Surg","first-page":"101","article-title":"Safety and efficacy of topical diclofenac and subcutaneous firocoxib, ketoprofen, and meloxicam in smoky jungle frogs (Leptodactylus pentadactylus)","volume":"30","author":"Balko JA","year":"2020","unstructured":"Balko JA, Posner LP, Ossiboff RJ, Chinnadurai SK. Safety and efficacy of topical diclofenac and subcutaneous firocoxib, ketoprofen, and meloxicam in smoky jungle frogs (Leptodactylus pentadactylus). J Herpetol Med Surg. 2020;30(2):101\u2013106. doi:10.5818\/18-04-151.1"},{"issue":"3","key":"B10","series-title":"J Am Assoc Lab Anim Sci","first-page":"355","article-title":"Analgesic effects of meloxicam, morphine sulfate, flunixin meglumine, and xylazine hydrochloride in African-clawed frogs (Xenopus laevis)","volume":"50","author":"Coble DJ","year":"2011","unstructured":"Coble DJ, Taylor DK, Mook DM. Analgesic effects of meloxicam, morphine sulfate, flunixin meglumine, and xylazine hydrochloride in African-clawed frogs (Xenopus laevis). J Am Assoc Lab Anim Sci. 2011;50(3):355\u2013360."},{"key":"B11","series-title":"Vet Med Int","first-page":"8863537","article-title":"Pharmacokinetics of transdermal flunixin meglumine following a single dose in marine toads (Rhinella marina)","volume":"2020","author":"Scott G","year":"2020","unstructured":"Scott G, Louis MM, Balko JA, et al. Pharmacokinetics of transdermal flunixin meglumine following a single dose in marine toads (Rhinella marina). Vet Med Int. 2020;2020:8863537. doi:10.1155\/2020\/8863537"},{"issue":"3","key":"B12","series-title":"J Vet Pharmacol Ther","first-page":"490","article-title":"Pharmacokinetics of multiple doses of transdermal flunixin meglumine in adult Holstein dairy cows","volume":"41","author":"Kleinhenz MD","year":"2018","unstructured":"Kleinhenz MD, Gorden PJ, Smith JS, et al. Pharmacokinetics of multiple doses of transdermal flunixin meglumine in adult Holstein dairy cows. J Vet Pharmacol Ther. 2018;41(3):490\u2013493. doi:10.1111\/jvp.12490"},{"issue":"7","key":"B13","series-title":"J Dairy Sci","first-page":"6418","article-title":"Effects of transdermal flunixin meglumine on experimentally induced lameness in adult dairy cattle","volume":"102","author":"Kleinhenz MD","year":"2019","unstructured":"Kleinhenz MD, Gorden PJ, Smith JS, et al. Effects of transdermal flunixin meglumine on experimentally induced lameness in adult dairy cattle. J Dairy Sci. 2019;102(7):6418\u20136430. doi:10.3168\/jds.2018-15091"},{"issue":"pt 11","key":"B14","series-title":"J Exp Biol","first-page":"2147","article-title":"Body wiping behaviors associated with cutaneous lipids in hylid tree frogs of Florida","volume":"208","author":"Barbeau TR","year":"2005","unstructured":"Barbeau TR, Lillywhite HB. Body wiping behaviors associated with cutaneous lipids in hylid tree frogs of Florida. J Exp Biol. 2005;208(pt 11):2147\u20132156. doi:10.1242\/jeb.01623"},{"issue":"3","key":"B15","series-title":"Biol Rev","first-page":"618","article-title":"From frog integument to human skin: dermatological perspectives from frog skin biology","volume":"89","author":"Haslam IS","year":"2014","unstructured":"Haslam IS, Roubos EW, Mangoni ML, et al. From frog integument to human skin: dermatological perspectives from frog skin biology. Biol Rev. 2014;89(3):618\u2013655. doi:10.1111\/brv.12072"},{"key":"B16","series-title":"Environ Toxicol Pharmacol","first-page":"5","article-title":"Regional variation in percutaneous absorption in the tree frog Litoria caerulea","volume":"60","author":"Llewelyn VK","year":"2018","unstructured":"Llewelyn VK, Berger L, Glass BD. Regional variation in percutaneous absorption in the tree frog Litoria caerulea. Environ Toxicol Pharmacol. 2018;60:5\u201311. doi:10.1016\/j.etap.2018.03.019"},{"issue":"1","key":"B17","series-title":"J Vet Pharmacol Ther","first-page":"91","article-title":"Percutaneous absorption between frog species: variability in skin may influence delivery of therapeutics","volume":"43","author":"Llewelyn VK","year":"2020","unstructured":"Llewelyn VK, Berger L, Glass BD. Percutaneous absorption between frog species: variability in skin may influence delivery of therapeutics. J Vet Pharmacol Ther. 2020;43(1):91\u201395. doi:10.1111\/jvp.12824"},{"issue":"11","key":"B18","series-title":"Animals","first-page":"3255","article-title":"Migration and histologic effects of visible implant elastomer (VIE) and passive integrated transponder (PIT) tags in the marine toad (Rhinella marina)","volume":"11","author":"Cabot ML","year":"2021","unstructured":"Cabot ML, Troan BV, Ange-van Heugten K, et al. Migration and histologic effects of visible implant elastomer (VIE) and passive integrated transponder (PIT) tags in the marine toad (Rhinella marina). Animals. 2021;11(11):3255. doi:10.3390\/ani11113255"},{"issue":"2","key":"B19","series-title":"J Vet Pharmacol Ther","first-page":"171","article-title":"Mathematical modeling and simulation in animal health. Part III: using nonlinear mixed-effects to characterize and quantify variability in drug pharmacokinetics","volume":"41","author":"Bon C","year":"2018","unstructured":"Bon C, Toutain PL, Concordet D, et al. Mathematical modeling and simulation in animal health. Part III: using nonlinear mixed-effects to characterize and quantify variability in drug pharmacokinetics. J Vet Pharmacol Ther. 2018;41(2):171\u2013183. doi:10.1111\/jvp.12473"},{"issue":"3","key":"B20","series-title":"J Zoo Wildl Med","first-page":"880","article-title":"Evaluation of the pharmacokinetic behavior of tulathromycin (Draxxin) in Florida manatees (Trichechus manatus latirostris) undergoing medical rehabilitation","volume":"52","author":"Smith LN","year":"2021","unstructured":"Smith LN, Bublitz C, Nixon E, Yeatts J, Ball RL, Baynes RE. Evaluation of the pharmacokinetic behavior of tulathromycin (Draxxin) in Florida manatees (Trichechus manatus latirostris) undergoing medical rehabilitation. J Zoo Wildl Med. 2021;52(3):880\u2013885. doi:10.1638\/2021-0025"},{"issue":"1","key":"B21","series-title":"J Am Vet Med Assoc","first-page":"1","article-title":"Popliteal sinus venipuncture in anurans","volume":"263","author":"Heniff AC","year":"2024","unstructured":"Heniff AC, Minter LJ, Balko JA, DeVoe RS. Popliteal sinus venipuncture in anurans. J Am Vet Med Assoc. 2024;263(1):1. doi:10.2460\/javma.24.07.0473"},{"issue":"7","key":"B22","series-title":"Metabolites","first-page":"776","article-title":"Transdermal flunixin meglumine as a pain relief in donkeys: a pharmacokinetics pilot study","volume":"13","author":"McLean AK","year":"2023","unstructured":"McLean AK, Falt T, Abdelfattah EM, et al. Transdermal flunixin meglumine as a pain relief in donkeys: a pharmacokinetics pilot study. Metabolites. 2023;13(7):776. doi:10.3390\/metabo13070776"},{"issue":"3","key":"B23","series-title":"J Vet Pharmacol Ther","first-page":"309","article-title":"Pharmacokinetics and pharmacodynamics of intravenous and transdermal flunixin meglumine in meat goats","volume":"42","author":"Reppert EJ","year":"2019","unstructured":"Reppert EJ, Kleinhenz MD, Montgomery SR, et al. Pharmacokinetics and pharmacodynamics of intravenous and transdermal flunixin meglumine in meat goats. J Vet Pharmacol Ther. 2019;42(3):309\u2013317. doi:10.1111\/jvp.12756"},{"issue":"6","key":"B24","series-title":"J Vet Pharmacol Ther","first-page":"612","article-title":"The pharmacokinetics of transdermal flunixin meglumine in Holstein calves","volume":"39","author":"Kleinhenz MD","year":"2016","unstructured":"Kleinhenz MD, Van Engen NK, Gorden PJ, et al. The pharmacokinetics of transdermal flunixin meglumine in Holstein calves. J Vet Pharmacol Ther. 2016;39(6):612\u2013615. doi:10.1111\/jvp.12314"},{"issue":"2","key":"B25","series-title":"J Am Assoc Lab Anim Sci","first-page":"202","article-title":"Comparison of etomidate, benzocaine, and MS222 anesthesia with and without subsequent flunixin meglumine analgesia in African clawed frogs (Xenopus laevis)","volume":"57","author":"Smith BD","year":"2018","unstructured":"Smith BD, Vail KJ, Carroll GL, et al. Comparison of etomidate, benzocaine, and MS222 anesthesia with and without subsequent flunixin meglumine analgesia in African clawed frogs (Xenopus laevis). J Am Assoc Lab Anim Sci. 2018;57(2):202\u2013209."},{"issue":"2","key":"B26","series-title":"Vet J","first-page":"218","article-title":"Transdermal drug delivery: basic principles for the veterinarian","volume":"172","author":"Mills PC","year":"2006","unstructured":"Mills PC, Cross SE. Transdermal drug delivery: basic principles for the veterinarian. Vet J. 2006;172(2):218\u2013233. doi:10.1016\/j.tvjl.2005.09.006"},{"issue":"2","key":"B27","series-title":"Environ Toxicol Chem","first-page":"361","article-title":"Effects of skin region and relative lipophilicity on percutaneous absorption in the toad Rhinella marina","volume":"38","author":"Llewelyn VK","year":"2019","unstructured":"Llewelyn VK, Berger L, Glass BD. Effects of skin region and relative lipophilicity on percutaneous absorption in the toad Rhinella marina. Environ Toxicol Chem. 2019;38(2):361\u2013367. doi:10.1002\/etc.4302"},{"issue":"2","key":"B28","series-title":"Molecules","first-page":"347","article-title":"Peptides for skin protection and healing in amphibians","volume":"24","author":"Demori I","year":"2019","unstructured":"Demori I, Rashed ZE, Corradino V, et al. Peptides for skin protection and healing in amphibians. Molecules. 2019;24(2):347. doi:10.3390\/molecules24020347"}],"container-title":["American Journal of Veterinary Research"],"original-title":[],"link":[{"URL":"https:\/\/avmajournals.avma.org\/view\/journals\/ajvr\/86\/5\/ajvr.24.12.0414.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/avmajournals.avma.org\/downloadpdf\/journals\/ajvr\/86\/5\/ajvr.24.12.0414.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/avmajournals.avma.org\/downloadpdf\/journals\/ajvr\/86\/5\/ajvr.24.12.0414.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T12:41:58Z","timestamp":1746103318000},"score":1,"resource":{"primary":{"URL":"https:\/\/avmajournals.avma.org\/view\/journals\/ajvr\/86\/5\/ajvr.24.12.0414.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,1]]},"references-count":28,"journal-issue":{"issue":"5"},"URL":"https:\/\/doi.org\/10.2460\/ajvr.24.12.0414","relation":{},"ISSN":["0002-9645","1943-5681"],"issn-type":[{"type":"print","value":"0002-9645"},{"type":"electronic","value":"1943-5681"}],"subject":[],"published":{"date-parts":[[2025,5,1]]}}}