{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T08:42:49Z","timestamp":1792226569444,"version":"4.4.0"},"reference-count":18,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    This Phase I study evaluated the safety, tolerability, and pharmacokinetics of a 30\u2010min topiramate injection (intravenous [IV] TPM) infusion compared with oral topiramate (oral TPM) in healthy adult participants. In this randomized, open\u2010label, dose escalation, crossover study with 37 healthy participants received single doses of 50, 100, or 200\u2009mg of an oral TPM tablet and an IV TPM formulation, using sulfobutylether beta\u2010cyclodextrin as a solubilizer and stabilizer, infused over 30\u2009min, with a 12\u2010day washout. Blood samples for pharmacokinetic assessments were collected at predose through 192\u2009h post dose. Concentration\u2013time data were analyzed using non\u2010compartmental analysis, and IV TPM relative bioavailability was determined. Topiramate injection AUC\n                    <jats:sub>inf<\/jats:sub>\n                    (total exposure) increased linearly with dose. The mean (90% confidence interval [CI]) relative bioavailability was 97.1% (94.6\u201399.7%). The mean (\u00b1 SD) clearance for 50, 100, and 200\u2009mg IV TPM was 1.4\u2009L\/h (\u00b10.2), 1.3\u2009L\/h (\u00b10.2), and 1.3\u2009L\/h (\u00b10.2), respectively. Half\u2010life was comparable across routes. Dose proportionality was demonstrated for AUC\n                    <jats:sub>inf<\/jats:sub>\n                    over the 50\u2013200\u2009mg range. No serious adverse events were reported. These findings suggest that when oral TPM administration is not feasible, equivalent doses of topiramate injection infused over 30\u2009min at intervals can temporarily replace oral dosing until it can be resumed.\n                  <\/jats:p>","DOI":"10.1002\/epi.70432","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T14:02:00Z","timestamp":1786370520000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Phase I study of the pharmacokinetics (\n                    <scp>PK<\/scp>\n                    ), bioavailability, dose proportionality, safety, and tolerability of topiramate injection compared to Oral topiramate in healthy adult participants"],"prefix":"10.1002","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2681-0899","authenticated-orcid":false,"given":"Adeboye O.","family":"Bamgboye","sequence":"first","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology, College of Pharmacy University of Minnesota  Minneapolis Minnesota USA"},{"name":"Center for Orphan Drug Research, College of Pharmacy University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3607-6619","authenticated-orcid":false,"given":"James C.","family":"Cloyd","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology, College of Pharmacy University of Minnesota  Minneapolis Minnesota USA"},{"name":"Center for Orphan Drug Research, College of Pharmacy University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard D.","family":"King","sequence":"additional","affiliation":[{"name":"Macnas Consulting International, Inc.  New Bern North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3613-9904","authenticated-orcid":false,"given":"Lisa D.","family":"Coles","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology, College of Pharmacy University of Minnesota  Minneapolis Minnesota USA"},{"name":"Center for Orphan Drug Research, College of Pharmacy University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)32596-0"},{"key":"e_1_2_13_3_1","unstructured":"Epilepsy: a public health imperative.https:\/\/www.who.int\/publications\/i\/item\/epilepsy\u2010a\u2010public\u2010health\u2010imperative"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12550"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a022426"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2019.05.051"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2021.108376"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40263-021-00827-8"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12134"},{"key":"e_1_2_13_10_1","unstructured":"U.S. Food and Drug Administration.VEKLURY\u00ae (remdesivir) for injection.2020.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2020\/214787Orig1s000lbl.pdf"},{"key":"e_1_2_13_11_1","unstructured":"U.S. Food and Drug Administration.KYPROLIS (carfilzomib) for injection [Internet].2021.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2021\/202714s033lbl.pdf"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.70244"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2005.01.001"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2016.10.020"},{"key":"e_1_2_13_15_1","unstructured":"Topamax (topiramate) tablets label. n.d.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2012\/020844s041lbl.pdf"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528\u20101167.2011.03183.x"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.51962"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S154388"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12165"}],"container-title":["Epilepsia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/epi.70432","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/epi.70432","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/epi.70432","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T08:27:21Z","timestamp":1792225641000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/epi.70432"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,10]]},"references-count":18,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1002\/epi.70432"],"URL":"https:\/\/doi.org\/10.1002\/epi.70432","archive":["Portico"],"relation":{},"ISSN":["0013-9580","1528-1167"],"issn-type":[{"value":"0013-9580","type":"print"},{"value":"1528-1167","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,10]]},"assertion":[{"value":"2026-04-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}