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Precision therapy with quinidine of KCNT1‐related epileptic disorders: A systematic review.

Authors :
Xu, Da
Chen, Shuang
Yang, Jun
Wang, Xiufeng
Fang, Zhi
Li, Man
Source :
British Journal of Clinical Pharmacology. Dec2022, Vol. 88 Issue 12, p5096-5112. 17p.
Publication Year :
2022

Abstract

Aims: Despite numerous studies on quinidine therapies for epilepsies associated with KCNT1 gene mutations, there is no consensus on its clinical utility. Thus, we reviewed studies evaluating the efficacy and safety of quinidine in KCNT1‐related epileptic disorders. Methods: Electronic databases were queried for in vivo and in vitro studies on quinidine therapy in KCNT1‐related epilepsies published on or before 1 May 2022. The evaluation of evidence was done as per the American Academy of Neurology's classification scheme. Identification of significant factors that possibly influenced therapeutic effects of quinidine were performed using χ2 tests. Results: Twenty‐seven studies containing 82 patient records were reviewed. Records of 80 patients with 33 KCNT1 mutations were analysed, of which 20 patients had gained ≥50% seizure reduction due to quinidine therapy. However, quinidine therapy often had different effects on patients with the same KCNT1 mutation. Age, genotypes of KCNT1 mutations, seizure types and brain MRI did not significantly influence the therapeutic effect of quinidine. Prolonged QTc was the most common among all adverse events with quinidine. Notably, results of in vitro quinidine tests did not correspond with in vivo tests. Conclusions: Therapeutic effects of quinidine on KCNT1‐related epilepsies remained indefinite as contradictory results were detected in similar patients. Age, seizure types, genotypes of KCNT1 mutations and brain MRI did not influence the therapeutic effects of quinidine. Insensitivity to quinidine by a certain Kcnt1 genotype in molecular tests is predictive of its inefficacy in human populations of the respective mutation. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
03065251
Volume :
88
Issue :
12
Database :
Academic Search Index
Journal :
British Journal of Clinical Pharmacology
Publication Type :
Academic Journal
Accession number :
160233220
Full Text :
https://doi.org/10.1111/bcp.15479