Michelline Joana Tenório Albuquerque Madruga Mesquita, Anne Caroline Silva Nogueira da Cruz, Rafael de Abreu Lima, Joana Tenório-Meireles, Arney José Nogueira Farias, Isabela Nogueira Santos, Gustavo Frota, Taciana Gabrielle Pinheiro de Moura Carvalho, Rafael Antônio Freire Carvalho, Jorge Antônio Meireles-Teixeira, Tereza Prazeres, Rafael Cardoso Carvalho, Maria do Socorro de Sousa Cartágenes, João Batista Santos Garcia
Background: Repositioning offers a cost-effective approach to discovering new therapeutic applications for existing medications. Ambroxol, primarily used as a mucolytic for respiratory diseases, has demonstrated anti-inflammatory, analgesic, and antioxidant properties, suggesting potential benefits in non-pulmonary conditions. This study conducted a systematic review to evaluate the efficacy of ambroxol in experimental disease models unrelated to the respiratory system.
Methods: Following registration in the Open Science Framework and adherence to the PICO strategy for formulating the guiding question, searches were performed in PUBMED/MEDLINE, EMBASE, and SCOPUS using the keywords: (Ambroxol) AND (Anti-Inflammatory Agents OR Analgesics OR Antioxidants) AND (Animals OR in vivo). The SYRCLE tool assessed methodological quality. Among 353 identified records, eight articles met eligibility criteria.
Results: These studies investigated ambroxol's effects in models of gastric lesions, neuropathic pain, psoriasis-like skin inflammation, hemorrhagic cystitis, and ischemia/reperfusion injuries in the liver and kidneys. Ambroxol doses ranged from 5 to 1000 mg/kg, predominantly administered orally. Its antioxidant properties were demonstrated by reducing free radicals and increasing enzymatic activity (SOD, CAT, GSH). Anti-inflammatory effects included a decrease in pro-inflammatory cytokines (TNF-α, IL-1β) and histological improvements. Antinociceptive action was observed through inhibition of voltage-gated sodium channels and reduction of oxidative stress, alleviating neuropathic pain.
Conclusions: Despite ambroxol's widespread clinical use, limited research has explored its non-respiratory applications. Existing studies suggest its promising therapeutic potential, reinforcing the need for further investigation into its role as an alternative treatment for various inflammatory and oxidative stress-related conditions beyond pulmonary diseases.
{"title":"Non-Pulmonary Mechanisms of Action of Ambroxol in In Vivo Experimental Models: a Systematic Review.","authors":"Michelline Joana Tenório Albuquerque Madruga Mesquita, Anne Caroline Silva Nogueira da Cruz, Rafael de Abreu Lima, Joana Tenório-Meireles, Arney José Nogueira Farias, Isabela Nogueira Santos, Gustavo Frota, Taciana Gabrielle Pinheiro de Moura Carvalho, Rafael Antônio Freire Carvalho, Jorge Antônio Meireles-Teixeira, Tereza Prazeres, Rafael Cardoso Carvalho, Maria do Socorro de Sousa Cartágenes, João Batista Santos Garcia","doi":"10.1111/fcp.70077","DOIUrl":"10.1111/fcp.70077","url":null,"abstract":"<p><strong>Background: </strong>Repositioning offers a cost-effective approach to discovering new therapeutic applications for existing medications. Ambroxol, primarily used as a mucolytic for respiratory diseases, has demonstrated anti-inflammatory, analgesic, and antioxidant properties, suggesting potential benefits in non-pulmonary conditions. This study conducted a systematic review to evaluate the efficacy of ambroxol in experimental disease models unrelated to the respiratory system.</p><p><strong>Methods: </strong>Following registration in the Open Science Framework and adherence to the PICO strategy for formulating the guiding question, searches were performed in PUBMED/MEDLINE, EMBASE, and SCOPUS using the keywords: (Ambroxol) AND (Anti-Inflammatory Agents OR Analgesics OR Antioxidants) AND (Animals OR in vivo). The SYRCLE tool assessed methodological quality. Among 353 identified records, eight articles met eligibility criteria.</p><p><strong>Results: </strong>These studies investigated ambroxol's effects in models of gastric lesions, neuropathic pain, psoriasis-like skin inflammation, hemorrhagic cystitis, and ischemia/reperfusion injuries in the liver and kidneys. Ambroxol doses ranged from 5 to 1000 mg/kg, predominantly administered orally. Its antioxidant properties were demonstrated by reducing free radicals and increasing enzymatic activity (SOD, CAT, GSH). Anti-inflammatory effects included a decrease in pro-inflammatory cytokines (TNF-α, IL-1β) and histological improvements. Antinociceptive action was observed through inhibition of voltage-gated sodium channels and reduction of oxidative stress, alleviating neuropathic pain.</p><p><strong>Conclusions: </strong>Despite ambroxol's widespread clinical use, limited research has explored its non-respiratory applications. Existing studies suggest its promising therapeutic potential, reinforcing the need for further investigation into its role as an alternative treatment for various inflammatory and oxidative stress-related conditions beyond pulmonary diseases.</p>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"40 2","pages":"e70077"},"PeriodicalIF":2.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12987714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147456466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maxime Demourgues, Julien Bezin, Romain Griffier, Antoine Pariente, Pernelle Noize, Sibylle de Germay
Background
Sodium glucose co-transporter type 2 inhibitors (SGLT2i) were initially developed as glucose-lowering drugs for diabetic patients. A few years after their market authorization in Europe, their indications were expanded to include first, heart failure (HF) and, subsequently, chronic kidney disease (CKD). These expansions led to a rapid increase in the use of this drug class and a diversification of the treated patient profile in the “real-life.”
Objectives
Describe in-hospital SGLT2i user profiles and evaluate compliance with guidelines.
Methods
A descriptive cross-sectional study was conducted using the Bordeaux University Hospital's clinical data warehouse. It included a random sample of 250 hospital stays of different patients with at least one administration of SGLT2i between February 1, 2022, and January 31, 2023. SGLT2i user profiles were described in terms of indications. Drug co-prescriptions were also described to evaluate compliance with guidelines.
Results
The majority of patients were aged 60–79 (59.6%), and were men (75.2%). HF was found in 87.2% of the patients treated with SGLT2i, followed by T2DM (45.2%) and CKD (21.2%). The most frequent indication profiles were HF without type II diabetes or CKD (42.0%) followed by HF and diabetes without CKD (26.0%). No patient had CKD as the sole indication. Prescriptions were considered compliant with guidelines for 76.4% of patients. Suboptimal prescriptions were mainly due to absence of another recommended drug without justification.
Conclusion
SGLT2i are now primarily used to treat HF. Their therapeutic potential in CKD appears to be still underestimated. Overall, compliance with guidelines appears satisfactory.
{"title":"SGLT-2 Inhibitors Use in Hospitalized Patients in France: A Cross-Sectional Study","authors":"Maxime Demourgues, Julien Bezin, Romain Griffier, Antoine Pariente, Pernelle Noize, Sibylle de Germay","doi":"10.1111/fcp.70076","DOIUrl":"10.1111/fcp.70076","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Sodium glucose co-transporter type 2 inhibitors (SGLT2i) were initially developed as glucose-lowering drugs for diabetic patients. A few years after their market authorization in Europe, their indications were expanded to include first, heart failure (HF) and, subsequently, chronic kidney disease (CKD). These expansions led to a rapid increase in the use of this drug class and a diversification of the treated patient profile in the “real-life.”</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Describe in-hospital SGLT2i user profiles and evaluate compliance with guidelines.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A descriptive cross-sectional study was conducted using the Bordeaux University Hospital's clinical data warehouse. It included a random sample of 250 hospital stays of different patients with at least one administration of SGLT2i between February 1, 2022, and January 31, 2023. SGLT2i user profiles were described in terms of indications. Drug co-prescriptions were also described to evaluate compliance with guidelines.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The majority of patients were aged 60–79 (59.6%), and were men (75.2%). HF was found in 87.2% of the patients treated with SGLT2i, followed by T2DM (45.2%) and CKD (21.2%). The most frequent indication profiles were HF without type II diabetes or CKD (42.0%) followed by HF and diabetes without CKD (26.0%). No patient had CKD as the sole indication. Prescriptions were considered compliant with guidelines for 76.4% of patients. Suboptimal prescriptions were mainly due to absence of another recommended drug without justification.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>SGLT2i are now primarily used to treat HF. Their therapeutic potential in CKD appears to be still underestimated. Overall, compliance with guidelines appears satisfactory.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"40 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147270802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Statin-induced liver injury is frequent and usually not severe. The aim of the present study was to describe the safety of statin rechallenge after atorvastatin-induced liver injury because it is poorly documented.
Methods
Cases of liver injury involving atorvastatin were selected from the French pharmacovigilance database. Inclusion criteria were a documented atorvastatin or any other statin reintroduction and an available follow-up of at least 2 weeks to define negative rechallenge.
Results
Twenty-six cases of atorvastatin liver injury with further statin reintroduction met our criteria. Median time to onset (TTO) of the first episode was 27 days (IQR: 4–43), with a cholestatic pattern in 11 (42.3%) cases, cytolytic in nine (34.6%), and mixed in six (23.1%); severity ranked Grade 2 in 11 (42.3%). Atorvastatin rechallenge was positive in 12 of 16 patients with the same dose (11 of 13) or a reduced dose (1 of 3), and the TTO was shorter (median 11 days). Rechallenge with an alternative statin was performed in 10 patients, of whom two experienced recurrence with rosuvastatin and simvastatin. No recurrence was observed after rechallenge of rosuvastatin in five, pravastatin in two, and simvastatin in one.
Conclusion
Our study evidenced frequent recurrence of drug-induced liver injury after atorvastatin rechallenge, whereas subsequent administration of a hydrophilic statin was well tolerated. By combining our data and published cases, we suggest that rosuvastatin or pravastatin carries the lowest risk of recurrence. Study limitations include a focus solely on atorvastatin, a retrospective design, and potential underreporting to the pharmacovigilance system.
{"title":"Atorvastatin-Associated Liver Injury: Outcome After Statin Rechallenge","authors":"Blandine Bertin, Valentine Lacotte, Jean-Luc Cracowski, Anais Gaiffe, Jérôme Dumortier, Thierry Vial","doi":"10.1111/fcp.70073","DOIUrl":"10.1111/fcp.70073","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Statin-induced liver injury is frequent and usually not severe. The aim of the present study was to describe the safety of statin rechallenge after atorvastatin-induced liver injury because it is poorly documented.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Cases of liver injury involving atorvastatin were selected from the French pharmacovigilance database. Inclusion criteria were a documented atorvastatin or any other statin reintroduction and an available follow-up of at least 2 weeks to define negative rechallenge.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Twenty-six cases of atorvastatin liver injury with further statin reintroduction met our criteria. Median time to onset (TTO) of the first episode was 27 days (IQR: 4–43), with a cholestatic pattern in 11 (42.3%) cases, cytolytic in nine (34.6%), and mixed in six (23.1%); severity ranked Grade 2 in 11 (42.3%). Atorvastatin rechallenge was positive in 12 of 16 patients with the same dose (11 of 13) or a reduced dose (1 of 3), and the TTO was shorter (median 11 days). Rechallenge with an alternative statin was performed in 10 patients, of whom two experienced recurrence with rosuvastatin and simvastatin. No recurrence was observed after rechallenge of rosuvastatin in five, pravastatin in two, and simvastatin in one.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study evidenced frequent recurrence of drug-induced liver injury after atorvastatin rechallenge, whereas subsequent administration of a hydrophilic statin was well tolerated. By combining our data and published cases, we suggest that rosuvastatin or pravastatin carries the lowest risk of recurrence. Study limitations include a focus solely on atorvastatin, a retrospective design, and potential underreporting to the pharmacovigilance system.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"40 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12906983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146201258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dupilumab is reimbursed in France for adult patients with moderate-to-severe atopic dermatitis (AD), in cases of failure, intolerance or contraindication to cyclosporin A (CsA). The French National Authority for Health requested collection of data on dupilumab-treated patients' characteristics and prior systemic treatments to examine conformity with the reimbursement scope.
Objectives
This study aimed to describe characteristics of adult patients initiating dupilumab for AD and their prior lines of systemic treatments with a focus on CsA.
Methods
Our dual approach combined information from two databases: the SNDS database allowing access to nationwide prescriptions for dupilumab (DUPIXAM study) and data collected by a sponsor-initiated multicentre, cross-sectional, observational study on patients initiating dupilumab for AD (MOVE study).
Results
From December 2019 to May 2021, 594 eligible patients were included in the MOVE study. In parallel, from March 2019 to December 2020, 3216 adult patients with presumed indications of moderate-to-severe AD were extracted from SNDS. Patients' characteristics were quite similar: median age was > 34 years old and they were gender balanced. More than 69% of MOVE patients had severe AD and 82.8% had at least one atopic comorbidities. Previous systemic treatments were used by over 62.8% of patients, of whom over 75.0% had received CsA. Among the 25.0% without previous CsA, the indirect combinatory approach made it possible to estimate an unbiased proportion of CsA contraindications in 71.0% of patients.
Conclusion
This joint analysis provided a detailed view of real-world conditions of dupilumab use in France through the completeness of data, and constitutes a proof of concept that could be extended to address other health-related questions.
{"title":"Real-World Use of Dupilumab in Atopic Dermatitis: Observational Study Results Linked to SNDS","authors":"Alain Dupuy, Anne-Claire Fougerousse, Pierre-André Bécherel, Catherine Droitcourt, Sandrine Kerbrat, Aymeric Mahieu, Noémie Allali, Anne-Lise Vataire, Claire Thénié, Nathalie Helman, Jean-Philippe Lacour","doi":"10.1111/fcp.70070","DOIUrl":"10.1111/fcp.70070","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Dupilumab is reimbursed in France for adult patients with moderate-to-severe atopic dermatitis (<span>AD</span>), in cases of failure, intolerance or contraindication to cyclosporin A (CsA). The French National Authority for Health requested collection of data on dupilumab-treated patients' characteristics and prior systemic treatments to examine conformity with the reimbursement scope.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>This study aimed to describe characteristics of adult patients initiating dupilumab for <span>AD</span> and their prior lines of systemic treatments with a focus on CsA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Our dual approach combined information from two databases: the SNDS database allowing access to nationwide prescriptions for dupilumab (DUPIXAM study) and data collected by a sponsor-initiated multicentre, cross-sectional, observational study on patients initiating dupilumab for <span>AD</span> (MOVE study).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>From December 2019 to May 2021, 594 eligible patients were included in the MOVE study. In parallel, from March 2019 to December 2020, 3216 adult patients with presumed indications of moderate-to-severe <span>AD</span> were extracted from SNDS. Patients' characteristics were quite similar: median age was > 34 years old and they were gender balanced. More than 69% of MOVE patients had severe <span>AD</span> and 82.8% had at least one atopic comorbidities. Previous systemic treatments were used by over 62.8% of patients, of whom over 75.0% had received CsA. Among the 25.0% without previous CsA, the indirect combinatory approach made it possible to estimate an unbiased proportion of CsA contraindications in 71.0% of patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This joint analysis provided a detailed view of real-world conditions of dupilumab use in France through the completeness of data, and constitutes a proof of concept that could be extended to address other health-related questions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"40 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chronic inflammation is involved in various mechanisms of memory impairment (MI). Although Janus kinase inhibitors (JAKi), which inhibit cytokine-induced JAK–STAT pathway, could theoretically protect against MI, we faced an unexpected case of MI in a non-elderly patient treated with JAKi.
Objective
Our study aims to investigate the association between JAKi and MI.
Methods
We searched VigiBase, the global pharmacovigilance database, for MI cases reported with JAKi from January 2011 to December 2023 and reviewed the literature for additional cases. The potential association was further explored through disproportionality analyses by calculating Reporting Odds Ratios (ROR), with statistical significance defined as a ROR and its 95% confidence interval exceeding 1.
Results
A total of 3788 MI cases associated with JAKi were included, 36.3% of which were serious. Over half involved non-elderly patients, and co-reported confounding drugs were rare. According to disproportionality analyses, MI was reported nearly three times more frequently with JAKi than with all other drugs (ROR 2.92; 95% CI: 2.83–3.01). To illustrate, a 54-year-old woman with rheumatoid arthritis treated with tofacitinib for 6 months experienced MI with word-finding difficulties (e.g., reduced categorical fluency: 25 animals named in 2 min; norm 30–47) and short-term memory loss, fully resolved 6 weeks post-discontinuation.
Conclusion
Our data support the positive association between MI and JAKi, potentially mediated through hippocampal JAK/STAT pathway inhibition, impairing cholinergic neurotransmission and synaptic plasticity. While further investigations are warranted to confirm or refute this pharmacovigilance signal, clinicians should remain vigilant given this potentially serious adverse effect.
{"title":"JAK Inhibitors and Memory Impairment: Disproportionality Analyses in the WHO Global Pharmacovigilance Database, VigiBase","authors":"Marilou Duboëlle, Adriano Lercara, Yves-Marie Pers, Céline Michel, Marion Lepelley, Marie-Blanche Valnet-Rabier, Jean-Luc Faillie, Virginie Bres, Pascale Palassin","doi":"10.1111/fcp.70072","DOIUrl":"10.1111/fcp.70072","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Chronic inflammation is involved in various mechanisms of memory impairment (MI). Although Janus kinase inhibitors (JAKi), which inhibit cytokine-induced JAK–STAT pathway, could theoretically protect against MI, we faced an unexpected case of MI in a non-elderly patient treated with JAKi.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Our study aims to investigate the association between JAKi and MI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We searched VigiBase, the global pharmacovigilance database, for MI cases reported with JAKi from January 2011 to December 2023 and reviewed the literature for additional cases. The potential association was further explored through disproportionality analyses by calculating Reporting Odds Ratios (ROR), with statistical significance defined as a ROR and its 95% confidence interval exceeding 1.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 3788 MI cases associated with JAKi were included, 36.3% of which were serious. Over half involved non-elderly patients, and co-reported confounding drugs were rare. According to disproportionality analyses, MI was reported nearly three times more frequently with JAKi than with all other drugs (ROR 2.92; 95% CI: 2.83–3.01). To illustrate, a 54-year-old woman with rheumatoid arthritis treated with tofacitinib for 6 months experienced MI with word-finding difficulties (e.g., reduced categorical fluency: 25 animals named in 2 min; norm 30–47) and short-term memory loss, fully resolved 6 weeks post-discontinuation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our data support the positive association between MI and JAKi, potentially mediated through hippocampal JAK/STAT pathway inhibition, impairing cholinergic neurotransmission and synaptic plasticity. While further investigations are warranted to confirm or refute this pharmacovigilance signal, clinicians should remain vigilant given this potentially serious adverse effect.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"40 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12819935/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146010054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Demirpolat, et al., Topical Probiotic Therapy Reduces Chemotherapy-Induced Oral Mucositis: Preclinical Evaluation in a Rat Model, Fundamental & Clinical Pharmacology2025, 39(6): e70050, https://doi.org/10.1111/fcp.70050.
Initially, Eren Demirpolat was mistakenly placed as the second author, although he should have been listed first according to contributorship. The author list has been revised as follows:
Eren Demirpolat1, Buse Kose Demirezen2, Arzu Yay3, Ozge Cengiz Mat4, Mustafa Ermis5
We apologize for this error.
deirpolat，等，局部益生菌治疗减少化疗诱导的口腔黏膜炎：大鼠模型的临床前评估，基础与临床药理，2015,39(6):e70050, https://doi.org/10.1111/fcp.70050。最初，即使Demirpolat也被错误地列为第二作者，尽管根据贡献，他应该被列为第一。作者名单修改如下：even Demirpolat 1， Buse Kose Demirezen 2, Arzu Yay 3, Ozge Cengiz Mat 4, Mustafa Ermis 5。我们为这个错误道歉。
{"title":"Correction to “Topical Probiotic Therapy Reduces Chemotherapy-Induced Oral Mucositis: Preclinical Evaluation in a Rat Model”","authors":"","doi":"10.1111/fcp.70071","DOIUrl":"10.1111/fcp.70071","url":null,"abstract":"<p>\u0000 <span>Demirpolat, </span> et al., <span>Topical Probiotic Therapy Reduces Chemotherapy-Induced Oral Mucositis: Preclinical Evaluation in a Rat Model</span>, <i>Fundamental & Clinical Pharmacology</i> <span>2025</span>, <span>39</span>(<span>6</span>): e70050, https://doi.org/10.1111/fcp.70050.\u0000 </p><p>Initially, Eren Demirpolat was mistakenly placed as the second author, although he should have been listed first according to contributorship. The author list has been revised as follows:</p><p>\u0000 <b>Eren Demirpolat</b>\u0000 <sup>\u0000 <b>1</b>\u0000 </sup>\u0000 <b>, Buse Kose Demirezen</b>\u0000 <sup>\u0000 <b>2</b>\u0000 </sup>\u0000 <b>, Arzu Yay</b>\u0000 <sup>\u0000 <b>3</b>\u0000 </sup>\u0000 <b>, Ozge Cengiz Mat</b>\u0000 <sup>\u0000 <b>4</b>\u0000 </sup>\u0000 <b>, Mustafa Ermis</b>\u0000 <sup>\u0000 <b>5</b>\u0000 </sup>\u0000 </p><p>We apologize for this error.</p>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"40 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/fcp.70071","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145932782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nicolas Picard, Estelle Ayme-Dietrich, Sylvie Quaranta, Tiphaine Adam-De-Beaumais, Abd El Kader Ait Tayeb, Hugo Alarcan, Dorra Amor, David Barthelemy, Mouna Ben Sassi, Séverine Cunat, Mouna Daldoul, Hervé Delacour, Marie-Christine Etienne-Grimaldi, Xavier Fonrose, Benjamin Hennart, Louis Lebreton, Stephanie Malard, Céline Narjoz, Asma Omezzine, Nicolas Pallet, Léa Payen, Jeanne Petit, Fabienne Thomas, Sameh Trabelsi, Camille Tron, Céline Verstuyft, Paul Vilquin, Jean-Christophe Boyer, Vincent Haufroid, French-Speaking Network of Pharmacogenetics (RNPGx)
Background
The implementation of pharmacogenetics in clinical practice increasingly relies on multigene panels.
Objectives
The objective of this study is to develop harmonized recommendations for the design and analytical implementation of multigene pharmacogenetic panels, defining clinically relevant genes and associated regions of interest (ROIs) based on evidence strength, therapeutic applicability, and compatibility with genotyping or sequencing technologies.
Methods
The French-Speaking Network of Pharmacogenetics (RNPGx) evaluated 81 candidate genes across five therapeutic domains (i.e., oncology and supportive care, anesthesia and pain management, cardiology, neurology and psychiatry and immunology and infectious diseases) using a structured, evidence-based scoring system. Each gene was evaluated using a 25-point scoring system integrating pharmacogenetic importance, regulatory and professional society recommendations, and expert consensus. For the genes ultimately selected for the core panel, clinically relevant regions of interest were defined and assigned to one of three analytical classes. Class 1 includes variants with established clinical actionability; Class 2 adds optional variants suitable for extended testing in specialized settings; and Class 3 covers broader genomic regions mainly intended for rare variant or structural analyses.
Results
A 28-gene core panel was retained. Class 1 included 76 prioritized variants (including CYP2D6 CNV variants), and Class 2 comprised 62 additional variants (with extended analysis for CYP2D6). Class 3 eligibility was retained for 18 genes.
Conclusion
The RNPGx recommendations offer a harmonized and flexible framework for pharmacogenetic panel design and for the extraction and interpretation of pharmacogenetic data from whole-exome or whole-genome sequencing.
{"title":"French-Speaking Network of Pharmacogenetics (RNPGx) Recommendations for Gene Panel Analysis Through Genotyping or Sequencing in Pharmacogenetics","authors":"Nicolas Picard, Estelle Ayme-Dietrich, Sylvie Quaranta, Tiphaine Adam-De-Beaumais, Abd El Kader Ait Tayeb, Hugo Alarcan, Dorra Amor, David Barthelemy, Mouna Ben Sassi, Séverine Cunat, Mouna Daldoul, Hervé Delacour, Marie-Christine Etienne-Grimaldi, Xavier Fonrose, Benjamin Hennart, Louis Lebreton, Stephanie Malard, Céline Narjoz, Asma Omezzine, Nicolas Pallet, Léa Payen, Jeanne Petit, Fabienne Thomas, Sameh Trabelsi, Camille Tron, Céline Verstuyft, Paul Vilquin, Jean-Christophe Boyer, Vincent Haufroid, French-Speaking Network of Pharmacogenetics (RNPGx)","doi":"10.1111/fcp.70068","DOIUrl":"10.1111/fcp.70068","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The implementation of pharmacogenetics in clinical practice increasingly relies on multigene panels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>The objective of this study is to develop harmonized recommendations for the design and analytical implementation of multigene pharmacogenetic panels, defining clinically relevant genes and associated regions of interest (ROIs) based on evidence strength, therapeutic applicability, and compatibility with genotyping or sequencing technologies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The French-Speaking Network of Pharmacogenetics (RNPGx) evaluated 81 candidate genes across five therapeutic domains (i.e., oncology and supportive care, anesthesia and pain management, cardiology, neurology and psychiatry and immunology and infectious diseases) using a structured, evidence-based scoring system. Each gene was evaluated using a 25-point scoring system integrating pharmacogenetic importance, regulatory and professional society recommendations, and expert consensus. For the genes ultimately selected for the core panel, clinically relevant regions of interest were defined and assigned to one of three analytical classes. Class 1 includes variants with established clinical actionability; Class 2 adds optional variants suitable for extended testing in specialized settings; and Class 3 covers broader genomic regions mainly intended for rare variant or structural analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A 28-gene core panel was retained. Class 1 included 76 prioritized variants (including CYP2D6 CNV variants), and Class 2 comprised 62 additional variants (with extended analysis for CYP2D6). Class 3 eligibility was retained for 18 genes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The RNPGx recommendations offer a harmonized and flexible framework for pharmacogenetic panel design and for the extraction and interpretation of pharmacogenetic data from whole-exome or whole-genome sequencing.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"40 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145905981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Receptor occupancy is an important indicator of drug efficacy. Pulsed drug delivery is aimed at accurately determining the dosing time on the basis of the onset rhythm.
Objective
Seeking analytical expressions to describe steady-state receptor occupancy and providing the essential principles that must be met when designing pulsed drug delivery.
Methods
We use a simplified model that integrates pharmacokinetics and binding kinetics to obtain analytical results.
Results
It was found that a Hill–Langmuir equation can integrate pharmacokinetics and pharmacodynamics and describe receptor occupancy under multiple-dose regimens and pulsed drug delivery without rapid equilibrium assumption. In this equation, the effective dissociation constant is the product of the elimination rate constant, the dosing interval, and the dissociation constant. Thus, the regulation of receptor occupancy by these three parameters has a mutual compensatory function. Regardless of the dosing regimen, the association rate constant mainly controls the rising rate and maximum receptor occupancy, whereas the dissociation rate constant determines the decline rate and maximum receptor occupancy and thus controls the stability of the binding kinetics. The regulation of receptor occupancy by the association and dissociation rate constants is consistent with the classical definition of binding affinity. These results may be useful for drug discovery.
Conclusion
When designing pulsed drug delivery, the elimination rate constant must be greater than the dose frequency. The association rate constant produces a fast effect, whereas the dissociation rate constant produces a slow but sustained effect.
{"title":"The Hill–Langmuir Equation Governs Drug–Target Binding Kinetics for Pulsed Drug Delivery","authors":"Xiaomin Shi","doi":"10.1111/fcp.70069","DOIUrl":"10.1111/fcp.70069","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Receptor occupancy is an important indicator of drug efficacy. Pulsed drug delivery is aimed at accurately determining the dosing time on the basis of the onset rhythm.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Seeking analytical expressions to describe steady-state receptor occupancy and providing the essential principles that must be met when designing pulsed drug delivery.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We use a simplified model that integrates pharmacokinetics and binding kinetics to obtain analytical results.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>It was found that a Hill–Langmuir equation can integrate pharmacokinetics and pharmacodynamics and describe receptor occupancy under multiple-dose regimens and pulsed drug delivery without rapid equilibrium assumption. In this equation, the effective dissociation constant is the product of the elimination rate constant, the dosing interval, and the dissociation constant. Thus, the regulation of receptor occupancy by these three parameters has a mutual compensatory function. Regardless of the dosing regimen, the association rate constant mainly controls the rising rate and maximum receptor occupancy, whereas the dissociation rate constant determines the decline rate and maximum receptor occupancy and thus controls the stability of the binding kinetics. The regulation of receptor occupancy by the association and dissociation rate constants is consistent with the classical definition of binding affinity. These results may be useful for drug discovery.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>When designing pulsed drug delivery, the elimination rate constant must be greater than the dose frequency. The association rate constant produces a fast effect, whereas the dissociation rate constant produces a slow but sustained effect.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"40 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145843550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zeinab Abbas, Clémence Lacroix, Elisabeth Jouve, Céline Eiden, Joelle Micallef, Hélène Peyrière, and the French Addictovigilance network
Background
The objective of this study was to assess the prevalence of dependence and abuse of psychoactive substances (PAS) among prison inmates, using data from the OPPIDUM program between 2013 and 2022.
Methods
OPPIDUM is an annual, cross-sectional national program, conducted among users consulting in specialised addiction centres. Prison inmates were questioned about their PAS use during the week preceding their incarceration. Two groups of participants were compared: prison inmates who reported simple use of PAS and those with abuse/dependence problems.
Results
A total of 2626 individuals responded to the program (men, 91.6%; mean age, 34.4 ± 9.30 years), reporting 5352 PAS. The main PAS consumed were cannabis (52.8%), cocaine/crack (28.6%), benzodiazepines (23.1%) and heroin (14.8%). Opioid substitution treatment (OST) was reported by 54.9% of participants. Several variables were associated with a significantly increased odds of abuse/dependence: intravenous use (OR, 4.608; 95% CI, 1.44–14.69; p = 0.01), PAS illegal acquisition (OR, 3.79; 95% CI, 2.19–6.58; p < 0.0001), heroin/speedball use (OR, 4.24; 95% CI, 1.16–15.48; p = 0.029) and cocaine/crack use (OR, 3.3; 95% CI, 1.47–7.39; p = 0.004). Conversely, being on OST protocol was associated with a lower odds of abuse/dependence (OR, 0.511; 95% CI, 0.28–0.93; p = 0.028).
Limitations and Conclusion
The main limitations of the study include self-reported PAS use without objective diagnoses, sometimes incomplete data on PAS use and incarceration and a sample biased toward inmates linked to substance abuse services, which likely overestimates the prevalence of PAS use. However, these results highlight the importance of assessing factors associated with substance abuse and dependence for appropriate prevention and management among prison inmates.
本研究的目的是利用2013年至2022年OPPIDUM项目的数据，评估监狱囚犯对精神活性物质（PAS）的依赖和滥用程度。方法OPPIDUM是一个年度、横断面的国家项目，在专门的成瘾中心对使用者进行咨询。监狱囚犯被询问了他们在被监禁前一周使用PAS的情况。研究人员对两组参与者进行了比较：报告单纯使用PAS的囚犯和有滥用/依赖问题的囚犯。结果共有2626人对该计划有反应（男性，91.6%，平均年龄34.4±9.30岁），报告5352 PAS。吸食大麻（52.8%）、可卡因/快克（28.6%）、苯二氮卓类药物（23.1%）和海洛因（14.8%）。54.9%的参与者报告了阿片替代治疗（OST）。有几个变量与滥用/依赖的几率显著增加有关：静脉注射（OR, 4.608; 95% CI, 1.44-14.69; p = 0.01），非法获取PAS (OR, 3.79; 95% CI, 2.19-6.58; p < 0.0001)，海洛因/速效球使用（OR, 4.24; 95% CI, 1.16-15.48; p = 0.029）和可卡因/快克使用（OR, 3.3; 95% CI, 1.47-7.39; p = 0.004）。相反，使用OST方案与较低的滥用/依赖几率相关（OR, 0.511; 95% CI, 0.28-0.93; p = 0.028）。该研究的主要局限性包括自我报告PAS使用情况而没有客观诊断，有时关于PAS使用和监禁的数据不完整，以及偏向于与药物滥用服务有关的囚犯的样本，这可能高估了PAS使用的普遍程度。然而，这些结果强调了评估与药物滥用和依赖有关的因素对监狱囚犯进行适当预防和管理的重要性。
{"title":"Use of Psychoactive Substances Before Incarceration Among Prison Inmates With Drug Abuse or Dependence: Data From the OPPIDUM Program","authors":"Zeinab Abbas, Clémence Lacroix, Elisabeth Jouve, Céline Eiden, Joelle Micallef, Hélène Peyrière, and the French Addictovigilance network","doi":"10.1111/fcp.70058","DOIUrl":"https://doi.org/10.1111/fcp.70058","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The objective of this study was to assess the prevalence of dependence and abuse of psychoactive substances (PAS) among prison inmates, using data from the OPPIDUM program between 2013 and 2022.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>OPPIDUM is an annual, cross-sectional national program, conducted among users consulting in specialised addiction centres. Prison inmates were questioned about their PAS use during the week preceding their incarceration. Two groups of participants were compared: prison inmates who reported simple use of PAS and those with abuse/dependence problems.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 2626 individuals responded to the program (men, 91.6%; mean age, 34.4 ± 9.30 years), reporting 5352 PAS. The main PAS consumed were cannabis (52.8%), cocaine/crack (28.6%), benzodiazepines (23.1%) and heroin (14.8%). Opioid substitution treatment (OST) was reported by 54.9% of participants. Several variables were associated with a significantly increased odds of abuse/dependence: intravenous use (OR, 4.608; 95% CI, 1.44–14.69; <i>p</i> = 0.01), PAS illegal acquisition (OR, 3.79; 95% CI, 2.19–6.58; <i>p</i> < 0.0001), heroin/speedball use (OR, 4.24; 95% CI, 1.16–15.48; <i>p</i> = 0.029) and cocaine/crack use (OR, 3.3; 95% CI, 1.47–7.39; <i>p</i> = 0.004). Conversely, being on OST protocol was associated with a lower odds of abuse/dependence (OR, 0.511; 95% CI, 0.28–0.93; <i>p</i> = 0.028).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Limitations and Conclusion</h3>\u0000 \u0000 <p>The main limitations of the study include self-reported PAS use without objective diagnoses, sometimes incomplete data on PAS use and incarceration and a sample biased toward inmates linked to substance abuse services, which likely overestimates the prevalence of PAS use. However, these results highlight the importance of assessing factors associated with substance abuse and dependence for appropriate prevention and management among prison inmates.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"40 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/fcp.70058","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145739878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Humbert de Freminville, Laura Lucatelli, Marc Chanelière, Guillaume Grenet, Sabine Mainbourg, Rémy Boussageon
Neuropathic pain remains a complex condition to manage. While current literature provides best practice guidelines for the use of gabapentinoids in this indication, these recommendations are primarily based on randomised clinical trials (RCTs) and meta-analyses of varying methodological quality. To support evidence-based prescribing, we conducted an evaluation of the overall confidence in meta-analytic findings on the efficacy of gabapentinoid in adults. A systematic review of the meta-analyses of RCTs retrieved from the MEDLINE (PubMed) database was performed. The methodological quality of these meta-analyses was assessed using the AMSTAR 2 tool (A MeaSurement Tool to Assess systematic Reviews) and compared when available with the quality of evidence determined by the GRADE approach. Among the 16 included meta-analyses, 14 were rated as having ‘critically low’ quality, one as ‘low’ and one as ‘moderate’ according to AMSTAR 2. GRADE and AMSTAR 2 assessments were both available for six meta-analyses, but only one yielded a concordant result. According to AMSTAR 2, the highest-quality meta-analysis was the one published in the Cochrane Database of Systematic Reviews and concluded that more participants had substantial benefit (at least 50% pain relief or patient global impression change very much improved) with gabapentin at 1200 mg daily or greater than with placebo (in postherpetic neuralgia: RR = 1.8 [95% CI 1.5 to 2.1] and in painful diabetic neuropathy: RR = 1.9 [95% CI 1.5 to 2.3]). One limitation of this work is the inconsistent use of the term neuropathic pain, which may be defined differently across studies.
神经性疼痛仍然是一种复杂的疾病。虽然目前的文献提供了加巴喷丁类药物用于该适应症的最佳实践指南，但这些建议主要基于随机临床试验（rct）和不同方法学质量的荟萃分析。为了支持循证处方，我们对加巴喷丁类药物对成人疗效的meta分析结果的总体置信度进行了评估。对从MEDLINE （PubMed）数据库中检索的随机对照试验的meta分析进行系统回顾。使用AMSTAR 2工具（评估系统评价的测量工具）评估这些荟萃分析的方法学质量，并在可用时与GRADE方法确定的证据质量进行比较。在纳入的16项荟萃分析中，根据AMSTAR 2, 14项被评为“极低”质量，1项被评为“低”质量，1项被评为“中等”质量。GRADE和AMSTAR 2评估均可用于6项荟萃分析，但只有一项得出了一致的结果。根据AMSTAR 2，质量最高的荟萃分析是发表在Cochrane系统评价数据库上的荟萃分析，得出的结论是，与安慰剂相比，每天1200mg或更大剂量的加巴喷丁有更多的参与者获得了实质性的益处（至少50%的疼痛缓解或患者整体印象改变非常改善）（疱疹后神经痛：RR = 1.8 [95% CI 1.5至2.1]，疼痛性糖尿病神经病变：RR = 1.9 [95% CI 1.5至2.3]）。这项工作的一个局限性是术语神经性疼痛的使用不一致，在不同的研究中可能有不同的定义。
{"title":"Gabapentinoids and Neuropathic Pain: Evaluation of the Quality of Randomised Controlled Trials: An Umbrella Review","authors":"Humbert de Freminville, Laura Lucatelli, Marc Chanelière, Guillaume Grenet, Sabine Mainbourg, Rémy Boussageon","doi":"10.1111/fcp.70052","DOIUrl":"https://doi.org/10.1111/fcp.70052","url":null,"abstract":"<div>\u0000 \u0000 <p>Neuropathic pain remains a complex condition to manage. While current literature provides best practice guidelines for the use of gabapentinoids in this indication, these recommendations are primarily based on randomised clinical trials (RCTs) and meta-analyses of varying methodological quality. To support evidence-based prescribing, we conducted an evaluation of the overall confidence in meta-analytic findings on the efficacy of gabapentinoid in adults. A systematic review of the meta-analyses of RCTs retrieved from the MEDLINE (PubMed) database was performed. The methodological quality of these meta-analyses was assessed using the AMSTAR 2 tool (A MeaSurement Tool to Assess systematic Reviews) and compared when available with the quality of evidence determined by the GRADE approach. Among the 16 included meta-analyses, 14 were rated as having ‘critically low’ quality, one as ‘low’ and one as ‘moderate’ according to AMSTAR 2. GRADE and AMSTAR 2 assessments were both available for six meta-analyses, but only one yielded a concordant result. According to AMSTAR 2, the highest-quality meta-analysis was the one published in the Cochrane Database of Systematic Reviews and concluded that more participants had substantial benefit (at least 50% pain relief or patient global impression change very much improved) with gabapentin at 1200 mg daily or greater than with placebo (in postherpetic neuralgia: RR = 1.8 [95% CI 1.5 to 2.1] and in painful diabetic neuropathy: RR = 1.9 [95% CI 1.5 to 2.3]). One limitation of this work is the inconsistent use of the term neuropathic pain, which may be defined differently across studies.</p>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"40 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145739879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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