{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T07:24:21Z","timestamp":1782545061950,"version":"3.54.5"},"reference-count":59,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,2,12]],"date-time":"2023-02-12T00:00:00Z","timestamp":1676160000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>For an antiseizure medication (ASM) to be effective in status epilepticus (SE), the drug should be administered intravenously (i.v.) to provide quick access to the brain. However, poor aqueous solubility is a major problem in the development of parenteral drug solutions. Given its multiple mechanisms of action, topiramate (TPM) is a promising candidate for the treatment of established or refractory SE, as supported by clinical studies using nasogastric tube TPM administration. However, TPM is not clinically available as a solution for i.v. administration, which hampers its use in the treatment of SE. Here, we describe a novel easy\u2010to\u2010use and easy\u2010to\u2010prepare i.v. TPM formulation using the U.S. Food and Drug Administration (FDA)\u2013approved excipient meglumine.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>During formulation development, we compared the solubility of TPM in bi\u2010distilled water with vs without a range of meglumine concentrations. Furthermore, the solubility of combinations of TPM and levetiracetam and TPM, levetiracetam, and atorvastatin in aqueous meglumine concentrations was determined. Subsequently, the pharmacokinetics and tolerability of meglumine\u2010based solutions of TPM and TPM combinations were evaluated in rats, including animals following fluid percussion injury or pilocarpine\u2010induced SE.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The amino sugar meglumine markedly enhances the aqueous solubility of TPM. A comparison with data on dissolving TPM using sulfobutylether\u2010\u03b2\u2010cyclodextrin (Captisol) demonstrates that meglumine is much more effective for dissolving TPM. Furthermore, meglumine can be used to prepare drug cocktails where TPM is co\u2010administered with another ASM for SE treatment. The tolerability studies of the meglumine\u2010based TPM solution and meglumine\u2010based TPM combinations in normal rats and the rat fluid percussion injury and pilocarpine\u2010induced SE models demonstrate excellent tolerability of the novel drug solutions. Preclinical studies on antiseizure efficacy in the SE model are underway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>In conclusion, the novel meglumine\u2010based solution of TPM presented here may be well suited for clinical development.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.17520","type":"journal-article","created":{"date-parts":[[2023,1,28]],"date-time":"2023-01-28T07:49:00Z","timestamp":1674892140000},"page":"888-899","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Preclinical pharmacokinetics and tolerability of a novel meglumine\u2010based parenteral solution of topiramate and topiramate combinations for treatment of status epilepticus"],"prefix":"10.1111","volume":"64","author":[{"given":"Chris","family":"Rundfeldt","sequence":"first","affiliation":[{"name":"PrevEp Inc.  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