{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T13:07:31Z","timestamp":1754399251493,"version":"3.38.0"},"reference-count":15,"publisher":"American Veterinary Medical Association (AVMA)","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ajvr"],"published-print":{"date-parts":[[2016,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n<jats:p><jats:bold>OBJECTIVE<\/jats:bold> To evaluate the pharmacokinetics of zonisamide following rectal administration of 20 or 30 mg\/kg suspended in sterile water or polyethylene glycol (PEG) to healthy dogs and determine whether either dose resulted in plasma zonisamide concentrations within the recommended therapeutic target range (10 to 40 \u03bcg\/mL).<\/jats:p>\n<jats:p><jats:bold>ANIMALS<\/jats:bold> 8 healthy mixed-breed dogs.<\/jats:p>\n<jats:p><jats:bold>PROCEDURES<\/jats:bold> Each dog received each of 2 doses (20 or 30 mg\/kg) of zonisamide suspended in each of 2 delivery substrates (sterile water or PEG) in a randomized crossover study with a 7-day washout period between phases. A blood sample was collected from each dog immediately before and at predetermined times for 48 hours after zonisamide administration. Plasma zonisamide concentrations were determined by high-performance liquid chromatography, and data were analyzed with a noncompartmental model.<\/jats:p>\n<jats:p><jats:bold>RESULTS<\/jats:bold> Mean maximum plasma concentration, time to maximum plasma concentration, mean residence time, and elimination half-life did not differ significantly among the 4 treatments. The mean maximum plasma concentration for all 4 treatments was less than the therapeutic target range. The mean \u00b1 SD area under the concentration-time curve for the 30 mg\/kg-in-water treatment (391.94 \u00b1 237.00 h\u2022\u03bcg\/mL) was significantly greater than that for the 20 mg\/kg-in-water (146.19 \u00b1 66.27 h\u2022\u03bcg\/mL) and 20 mg\/kg-in-PEG (87.09 \u00b1 96.87 h\u2022\u03bcg\/mL) treatments.<\/jats:p>\n<jats:p><jats:bold>CONCLUSIONS AND CLINICAL RELEVANCE<\/jats:bold> Results indicated that rectal administration of zonisamide at doses of 20 and 30 mg\/kg failed to achieve plasma zonisamide concentrations within the recommended therapeutic target range. Therefore, rectal administration of zonisamide cannot be recommended as a suitable alternative to oral administration.<\/jats:p>","DOI":"10.2460\/ajvr.77.12.1374","type":"journal-article","created":{"date-parts":[[2016,11,30]],"date-time":"2016-11-30T14:18:03Z","timestamp":1480515483000},"page":"1374-1380","source":"Crossref","is-referenced-by-count":2,"title":["Pharmacokinetics of zonisamide following rectal administration to healthy dogs"],"prefix":"10.2460","volume":"77","author":[{"given":"Jennifer R.","family":"Michaels","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy J.","family":"Hodshon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William B.","family":"Thomas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dawn M.","family":"Boothe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lindsay","family":"Williams","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1272","reference":[{"key":"ref1","series-title":"A practical guide to canine and feline neurology","first-page":"237","article-title":"Seizures and narcolepsy","author":"Thomas","year":"2008"},{"key":"ref2","series-title":"J Am Anim Hosp Assoc","doi-asserted-by":"publisher","first-page":"285","DOI":"10.5326\/0400285","article-title":"Zonisamide therapy for refractory idiopathic epilepsy in dogs","volume":"40","author":"Dewey","year":"2004"},{"key":"ref3","series-title":"J Small Anim Pract","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1111\/j.1748-5827.2006.00290.x","article-title":"Prospective study of zonisamide therapy for refractory idiopathic epilepsy in dogs","volume":"48","author":"Von Klopmann","year":"2007"},{"key":"ref4","series-title":"J Vet Pharmacol Ther","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1111\/j.1365-2885.2008.00993.x","article-title":"Disposition and safety of zonisamide after intravenous and oral single dose and oral multiple dosing in normal hound dogs","volume":"31","author":"Boothe","year":"2008"},{"key":"ref5","series-title":"N Z Vet J","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1080\/00480169.2012.680855","article-title":"Zonisamide monotherapy for idiopathic epilepsy in dogs","volume":"60","author":"Chung","year":"2012"},{"key":"ref6","series-title":"Fundam Appl Toxicol","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1016\/0272-0590(88)90158-3","article-title":"Chronic toxicity of the anticonvulsant zonisamide in Beagle dogs","volume":"11","author":"Walker","year":"1988"},{"key":"ref7","series-title":"Vet Dermatol","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1111\/vde.12237","article-title":"Erythema multiforme associated with zonisamide in a dog","volume":"26","author":"Ackerman","year":"2015"},{"key":"ref8","series-title":"J Vet Intern Med","doi-asserted-by":"publisher","first-page":"1156","DOI":"10.1111\/j.1939-1676.2011.00783.x","article-title":"Apparent acute idiosyncratic hepatic necrosis associated with zonisamide administration in a dog","volume":"25","author":"Miller","year":"2011"},{"key":"ref9","series-title":"J Vet Med Sci","doi-asserted-by":"publisher","first-page":"1505","DOI":"10.1292\/jvms.11-0164","article-title":"Possible drug-induced hepatopathy in a dog receiving zonisamide monotherapy for treatment of cryptogenic epilepsy","volume":"73","author":"Schwartz","year":"2011"},{"key":"ref10","series-title":"J Vet Intern Med","doi-asserted-by":"publisher","first-page":"1454","DOI":"10.1111\/j.1939-1676.2011.00801.x","article-title":"Renal tubular acidosis associated with zonisamide therapy in a dog","volume":"25","author":"Cook","year":"2011"},{"key":"ref11","series-title":"J Vet Pharmacol Ther","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1111\/j.1365-2885.2009.01097.x","article-title":"Steady-state pharmacokinetics of zonisamide in plasma, whole blood and erythrocytes in dogs","volume":"33","author":"Fukunaga","year":"2010"},{"key":"ref12","series-title":"Biol Pharm Bull","doi-asserted-by":"publisher","first-page":"892","DOI":"10.1248\/bpb.20.892","article-title":"Utility of a rectal suppository containing the antiepileptic drug zonisamide","volume":"20","author":"Nagatomi","year":"1997"},{"key":"ref13","series-title":"J Vet Pharmacol Ther","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1111\/j.1365-2885.2008.00955.x","article-title":"Pharmacokinetics of zonisamide and drug interaction with phenobarbital in dogs","volume":"31","author":"Orito","year":"2008"},{"key":"ref14","series-title":"J Vet Intern Med","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1111\/jvim.12540","article-title":"Pharmacokinetics of single-dose rectal zonisamide administration in normal dogs","volume":"29","author":"Brewer","year":"2015"},{"key":"ref15","series-title":"J Vet Intern Med","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1111\/jvim.12269","article-title":"Levetiracetam rectal administration in healthy dogs","volume":"28","author":"Peters","year":"2014"}],"container-title":["American Journal of Veterinary Research"],"original-title":[],"link":[{"URL":"https:\/\/avmajournals.avma.org\/view\/journals\/ajvr\/77\/12\/ajvr.77.12.1374.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/avmajournals.avma.org\/downloadpdf\/journals\/ajvr\/77\/12\/ajvr.77.12.1374.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/avmajournals.avma.org\/downloadpdf\/journals\/ajvr\/77\/12\/ajvr.77.12.1374.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T12:37:36Z","timestamp":1741351056000},"score":1,"resource":{"primary":{"URL":"https:\/\/avmajournals.avma.org\/view\/journals\/ajvr\/77\/12\/ajvr.77.12.1374.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,12]]},"references-count":15,"journal-issue":{"issue":"12"},"URL":"https:\/\/doi.org\/10.2460\/ajvr.77.12.1374","relation":{},"ISSN":["0002-9645"],"issn-type":[{"type":"print","value":"0002-9645"}],"subject":[],"published":{"date-parts":[[2016,12]]}}}