{"title":"预测氟吡汀肝毒性的随机临床试验信号：系统评价。","authors":"Mahir Fidahic, Emilija Lozo Vukovac, Ewa Balkowiec-Iskra, Darko Krnic, Adriana Andric, Zeljana Margan Koletic, Livia Puljak","doi":"10.1007/s00228-025-03840-8","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The aim of this study was to systematically review clinical trials evaluating the flupirtine to identify any biochemical or clinical indicators that could signal serious hepatotoxicity.</p><p><strong>Methods: </strong>This systematic review included randomized controlled trials (RCTs) evaluating flupirtine-containing medicines for any clinical condition. Trials involving any population, comparator, or outcome were considered eligible for inclusion. A comprehensive search was conducted in Embase, MEDLINE, and CENTRAL from their inception until August 14, 2023. The risk of bias (RoB) in the included trials was assessed using Cochrane's 2011 RoB tool. Due to the heterogeneity of the included trials, a meta-analysis could not be performed.</p><p><strong>Results: </strong>A total of 35 trials published between 1983 and 2022 were included in this systematic review, with 1408 participants receiving flupirtine. Only five trials reported any data related to liver function tests. Among these, four trials documented transient, asymptomatic liver abnormalities that returned to normal after the trial period, while one trial was prematurely terminated. One trial reported normal liver test results in all participants. Of the three trials published after 2018, only one acknowledged the withdrawal of flupirtine from the European market. The majority of risk of bias (RoB) domains were classified as having an unclear risk of bias.</p><p><strong>Conclusion: </strong>Published RCTs did not report any evidence of serious hepatotoxicity associated with flupirtine based on the available biochemical or clinical data. However, liver function test results were reported in only 5 out of 35 included trials. Published RCTs are not reliable information about flupirtine-related hepatotoxicity.</p><p><strong>Registration: </strong>Protocol was published in PROSPERO (CRD42018085123).</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.4000,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Signals from randomized clinical trials predicting hepatotoxicity of flupirtine: systematic review.\",\"authors\":\"Mahir Fidahic, Emilija Lozo Vukovac, Ewa Balkowiec-Iskra, Darko Krnic, Adriana Andric, Zeljana Margan Koletic, Livia Puljak\",\"doi\":\"10.1007/s00228-025-03840-8\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The aim of this study was to systematically review clinical trials evaluating the flupirtine to identify any biochemical or clinical indicators that could signal serious hepatotoxicity.</p><p><strong>Methods: </strong>This systematic review included randomized controlled trials (RCTs) evaluating flupirtine-containing medicines for any clinical condition. Trials involving any population, comparator, or outcome were considered eligible for inclusion. A comprehensive search was conducted in Embase, MEDLINE, and CENTRAL from their inception until August 14, 2023. The risk of bias (RoB) in the included trials was assessed using Cochrane's 2011 RoB tool. Due to the heterogeneity of the included trials, a meta-analysis could not be performed.</p><p><strong>Results: </strong>A total of 35 trials published between 1983 and 2022 were included in this systematic review, with 1408 participants receiving flupirtine. Only five trials reported any data related to liver function tests. Among these, four trials documented transient, asymptomatic liver abnormalities that returned to normal after the trial period, while one trial was prematurely terminated. One trial reported normal liver test results in all participants. Of the three trials published after 2018, only one acknowledged the withdrawal of flupirtine from the European market. The majority of risk of bias (RoB) domains were classified as having an unclear risk of bias.</p><p><strong>Conclusion: </strong>Published RCTs did not report any evidence of serious hepatotoxicity associated with flupirtine based on the available biochemical or clinical data. However, liver function test results were reported in only 5 out of 35 included trials. Published RCTs are not reliable information about flupirtine-related hepatotoxicity.</p><p><strong>Registration: </strong>Protocol was published in PROSPERO (CRD42018085123).</p>\",\"PeriodicalId\":11857,\"journal\":{\"name\":\"European Journal of Clinical Pharmacology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":2.4000,\"publicationDate\":\"2025-04-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Journal of Clinical Pharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s00228-025-03840-8\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Clinical Pharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00228-025-03840-8","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Signals from randomized clinical trials predicting hepatotoxicity of flupirtine: systematic review.
Background: The aim of this study was to systematically review clinical trials evaluating the flupirtine to identify any biochemical or clinical indicators that could signal serious hepatotoxicity.
Methods: This systematic review included randomized controlled trials (RCTs) evaluating flupirtine-containing medicines for any clinical condition. Trials involving any population, comparator, or outcome were considered eligible for inclusion. A comprehensive search was conducted in Embase, MEDLINE, and CENTRAL from their inception until August 14, 2023. The risk of bias (RoB) in the included trials was assessed using Cochrane's 2011 RoB tool. Due to the heterogeneity of the included trials, a meta-analysis could not be performed.
Results: A total of 35 trials published between 1983 and 2022 were included in this systematic review, with 1408 participants receiving flupirtine. Only five trials reported any data related to liver function tests. Among these, four trials documented transient, asymptomatic liver abnormalities that returned to normal after the trial period, while one trial was prematurely terminated. One trial reported normal liver test results in all participants. Of the three trials published after 2018, only one acknowledged the withdrawal of flupirtine from the European market. The majority of risk of bias (RoB) domains were classified as having an unclear risk of bias.
Conclusion: Published RCTs did not report any evidence of serious hepatotoxicity associated with flupirtine based on the available biochemical or clinical data. However, liver function test results were reported in only 5 out of 35 included trials. Published RCTs are not reliable information about flupirtine-related hepatotoxicity.
Registration: Protocol was published in PROSPERO (CRD42018085123).
期刊介绍：
The European Journal of Clinical Pharmacology publishes original papers on all aspects of clinical pharmacology and drug therapy in humans. Manuscripts are welcomed on the following topics: therapeutic trials, pharmacokinetics/pharmacodynamics, pharmacogenetics, drug metabolism, adverse drug reactions, drug interactions, all aspects of drug development, development relating to teaching in clinical pharmacology, pharmacoepidemiology, and matters relating to the rational prescribing and safe use of drugs. Methodological contributions relevant to these topics are also welcomed.
Data from animal experiments are accepted only in the context of original data in man reported in the same paper. EJCP will only consider manuscripts describing the frequency of allelic variants in different populations if this information is linked to functional data or new interesting variants. Highly relevant differences in frequency with a major impact in drug therapy for the respective population may be submitted as a letter to the editor.
Straightforward phase I pharmacokinetic or pharmacodynamic studies as parts of new drug development will only be considered for publication if the paper involves
-a compound that is interesting and new in some basic or fundamental way, or
-methods that are original in some basic sense, or
-a highly unexpected outcome, or
-conclusions that are scientifically novel in some basic or fundamental sense.
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