The potential of intravenous topiramate for the treatment of status epilepticus

Löscher, Wolfgang; Trinka, Eugen

doi:10.1016/j.yebeh.2022.109032

Cited by 3 publications

(4 citation statements)

References 62 publications

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“…Based on studies with oral or nasogastric tube administration of TPM or administration by percutaneous endoscopic gastrostomy, the clinical perspective of an i.v. TPM solution for the treatment of SE or RSE is promising 7–9,47,50 . In clinical practice, TPM has been used when first‐ or second‐line ASMs failed to terminate SE 7 .…”

Section: Discussionmentioning

confidence: 99%

“…TPM solution for the treatment of SE or RSE is promising. [7][8][9]47,50 In clinical TPM has been used when or second-line ASMs failed to SE. 7 For the treatment of RSE, in one retrospective study, TPM successfully terminated RSE in over 70% of patients when it was given as the fourth to seventh ASM, 50 although another study did not observe such high efficacy.…”

Section: Meglumine-based Solutionsmentioning

confidence: 99%

“…Indeed, several clinical studies indicate that oral and nasogastric tube TPM administration may ameliorate RSE. [7][8][9][10] However, TPM is not clinically available as a solution for intravenous (i.v.) administration, which hampers its use in the treatment of SE.…”

Section: Introductionmentioning

confidence: 99%

“…Based on its multiple mechanisms of action, TPM is a promising candidate for the treatment of benzodiazepine (BDZ)–resistant (established) status epilepticus (SE) and SE that fails to respond to BDZ and at least one other ASM, a condition termed refractory SE (RSE). Indeed, several clinical studies indicate that oral and nasogastric tube TPM administration may ameliorate RSE 7–10 . However, TPM is not clinically available as a solution for intravenous (i.v.)…”

Section: Introductionmentioning

confidence: 99%

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Preclinical pharmacokinetics and tolerability of a novel meglumine‐based parenteral solution of topiramate and topiramate combinations for treatment of status epilepticus

Rundfeldt¹,

Klein

Boison

et al. 2023

Epilepsia

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Objective: 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-to-use and easy-to-prepare i.v. TPM formulation using the U.S. Food and Drug Administration (FDA)-approved excipient meglumine. Methods:During formulation development, we compared the solubility of TPM in bi-distilled 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-based solutions of TPM and TPM combinations were evaluated in rats, including animals following fluid percussion injury or pilocarpine-induced SE. Results:The amino sugar meglumine markedly enhances the aqueous solubility of TPM. A comparison with data on dissolving TPM using sulfobutylether-βcyclodextrin (Captisol) demonstrates that meglumine is much more effective for dissolving TPM. Furthermore, meglumine can be used to prepare drug cocktails where TPM is co-administered with another ASM for SE treatment. The tolerability studies of the meglumine-based TPM solution and meglumine-based TPM combinations in normal rats and the rat fluid percussion injury and pilocarpineinduced SE models demonstrate excellent tolerability of the novel drug solutions.Preclinical studies on antiseizure efficacy in the SE model are underway.

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Section: Discussionmentioning

confidence: 99%

Section: Meglumine-based Solutionsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Preclinical pharmacokinetics and tolerability of a novel meglumine‐based parenteral solution of topiramate and topiramate combinations for treatment of status epilepticus

Rundfeldt¹,

Klein

Boison

et al. 2023

Epilepsia

Self Cite

View full text Add to dashboard Cite

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Evaluation of Immune Function Enhancement and Clinical Symptom Alleviation in Epilepsy Patients Post-Topiramate Administration

Yuxiang Liu,

Liu,

Zhu

2024

Neurochem. J.

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An Insight-Based Computational Approaches to Estimate Molecular Weight Distribution, Allergenicity and Immunological Aspects, Toxicity Profile, Possible Biodegradation, Persistence and Bioaccumulation Factor of Four Phyto-Compounds

Bensaad,

Kahoul,

Khier

et al. 2023

j biobased mat bioenergy

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Clinical pharmacology and toxicology are considered nowadays two complementary and indispensable medical disciplines that allowed clinicians to achieve the optimal therapeutic effect of a several substance, but also to characterize their toxicity threshold. The contribution of bioinformatics tools and databases in these two fields has provided key elements, sometimes impossible to explain during early clinical phases. In this context, some computational approaches were used in this work to investigate the molecular weight distribution (MWD), allergenicity, toxicity profile, possible biodegradation, persistence and bioaccumulation factor of four natural compounds. Results revealed that MWD indices of compound 2 and 3 were the best among the tested compounds. However, the route of administration of compound 1 could be considered the safest for rats, especially the oral, intravenous and subcutaneous ways, in which LD50 values were the best, comparing to the other compounds. The two allergenicity tests revealed that the four phyto-compounds could be considered non-allergen agents and may not present any drug toxicity risks. Concerning cytotoxicity, compound 4 exhibited the best cytotoxic effect among these compounds with a corresponding value of Pa = 0.782 against colon carcinoma (HCT-116) cell line. The four bio-compounds could be toxic for avian species but non-toxic for Daphnia magna, a key aquatic species. Compound 1 exhibited the lowest bioaccumulation factor value (0.17). All compounds were inactive against Tox21-Stress response pathways, but compound 2 and 3 could potentially be immunotoxic. Finally, all tested compounds may possess a non persistent profile, while only compound 1 and 4 could possibly be biodegradable. This preliminary work, revealed once again the potential of phyto-compounds and certain fundamental aspects, which could represents an initial step for further investigation.

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The potential of intravenous topiramate for the treatment of status epilepticus

Cited by 3 publications

References 62 publications

Preclinical pharmacokinetics and tolerability of a novel meglumine‐based parenteral solution of topiramate and topiramate combinations for treatment of status epilepticus

Preclinical pharmacokinetics and tolerability of a novel meglumine‐based parenteral solution of topiramate and topiramate combinations for treatment of status epilepticus

Evaluation of Immune Function Enhancement and Clinical Symptom Alleviation in Epilepsy Patients Post-Topiramate Administration

An Insight-Based Computational Approaches to Estimate Molecular Weight Distribution, Allergenicity and Immunological Aspects, Toxicity Profile, Possible Biodegradation, Persistence and Bioaccumulation Factor of Four Phyto-Compounds

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