Fundamental & Clinical Pharmacology最新文献

{"title":"Medical Cannabis Use in France: An Observational Safety Study Based on the RECANN Registry and the Pharmacovigilance/Addictovigilance System From 2021 to 2024","authors":"Cécile Chevallier,&nbsp;Anne Batisse,&nbsp;Emilie Monzon,&nbsp;Nathalie Richard,&nbsp;Nicolas Authier,&nbsp;Chouki Chenaf,&nbsp;Louise Gaboriau,&nbsp;Véronique Ferey,&nbsp;Basile Chretien,&nbsp;Sophie Fedrizzi,&nbsp;Marine Auffret","doi":"10.1111/fcp.70074","DOIUrl":"10.1111/fcp.70074","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The French National Agency for Medicines and Health Products Safety implemented in 2021 a nationwide experimentation for medical cannabis (MC), designed to assess the feasibility of implementing a new public health policy. A dedicated registry was established to support the notification of adverse drug reactions (ADRs). The objective of this study was to describe the safety data collected during the first 3 years of experimentation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>Data related to MC use were extracted from the registry and the French pharmacovigilance and addictovigilance database between March 26, 2021, and March 31, 2024.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Result</h3>\u0000 \u0000 <p>Among the 3164 included patients, at least one ADR was reported in 1186 patients, including 81 patients (3%) with serious ADRs (SADRs). The most common ADRs were neurological (37.2%), gastrointestinal (16.9%), and psychiatric (15.2%). Among SADRs, six cases of acute coronary syndromes were reported, along with eight cases of suicidal thoughts including one suicide attempt. Half of these psychiatric events occurred in patients without a prior psychiatric history, and no cases of psychosis were documented. Regarding addictovigilance, only 12 ADRs were analyzed: seven withdrawal syndromes, three cases of tolerance, and two cases of THC-containing inflorescence misuse, including one case of MC use disorder.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>During the experimentation, 3% of patients treated with MC experienced at least one serious ADR. The safety profile was dominated by neurological, gastrointestinal, and psychiatric ADRs. Only one case of MC misuse was identified with inflorescences. This study is observational and non-comparative and cannot provide a comprehensive assessment of the risk associated with MC use.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"40 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147283344","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}

{"title":"Immunomodulatory Effects of Hyoscine Butylbromide on Mammalian Macrophages","authors":"Begüm Rana Atalay,&nbsp;Batuhan Yurtseven,&nbsp;Ebru Akbaba,&nbsp;Furkan Ayaz,&nbsp;Esra Aydemir","doi":"10.1111/fcp.70075","DOIUrl":"10.1111/fcp.70075","url":null,"abstract":"<div>\u0000 \u0000 <p>Hyoscine butylbromide (HB), popularly known as Buscopan, is a common anticholinergic antispasmodic used worldwide for gastrointestinal disorders. While the interaction between the cholinergic system and immunity is increasingly recognized, the direct immunomodulatory potential of HB on macrophages remains underexplored. Therefore, this study aimed to investigate whether HB exhibits immunomodulatory properties on a mammalian macrophage cell line, J774.2, in vitro. Proinflammatory cytokine production (TNF-α, IL-6, GM-CSF, and IL-12p40) in LPS-stimulated macrophages was quantified by ELISA. Based on the obtained results, it could be determined that HB did not affect cell viability at the tested concentrations. However, HB revealed a comparatively strong anti-inflammatory effect in LPS-stimulated macrophages. Our findings reveal that HB significantly and dose-dependently reduces IL-12p40, TNF-α, and IL-6 levels, with the most profound inhibition observed in IL-12p40 (<i>p</i> &lt; 0.001). Surprisingly, no significant effect was observed on the levels of GM-CSF. Such selective modulation implies that the effect of HB targets specific inflammatory signaling pathways—most likely by the blockade of nonneuronal muscarinic receptors—rather than causing general suppression of cytokine release. These findings suggest that HB, besides being an effective muscle relaxant, possesses intrinsic anti-inflammatory potential that can modulate immune responses. Identifying the specific cytokine-suppressing effect of HB illuminates its broader clinical profile and lays a sound foundation for its use in inflammatory gastrointestinal conditions such as irritable bowel syndrome (IBS). This study fills a critical gap in the literature on the immunomodulatory effect of hyoscine butylbromide.</p>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"40 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147270846","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}

{"title":"SGLT-2 Inhibitors Use in Hospitalized Patients in France: A Cross-Sectional Study","authors":"Maxime Demourgues,&nbsp;Julien Bezin,&nbsp;Romain Griffier,&nbsp;Antoine Pariente,&nbsp;Pernelle Noize,&nbsp;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}

{"title":"Atorvastatin-Associated Liver Injury: Outcome After Statin Rechallenge","authors":"Blandine Bertin,&nbsp;Valentine Lacotte,&nbsp;Jean-Luc Cracowski,&nbsp;Anais Gaiffe,&nbsp;Jérôme Dumortier,&nbsp;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}

{"title":"Real-World Use of Dupilumab in Atopic Dermatitis: Observational Study Results Linked to SNDS","authors":"Alain Dupuy,&nbsp;Anne-Claire Fougerousse,&nbsp;Pierre-André Bécherel,&nbsp;Catherine Droitcourt,&nbsp;Sandrine Kerbrat,&nbsp;Aymeric Mahieu,&nbsp;Noémie Allali,&nbsp;Anne-Lise Vataire,&nbsp;Claire Thénié,&nbsp;Nathalie Helman,&nbsp;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 &gt; 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}

{"title":"JAK Inhibitors and Memory Impairment: Disproportionality Analyses in the WHO Global Pharmacovigilance Database, VigiBase","authors":"Marilou Duboëlle,&nbsp;Adriano Lercara,&nbsp;Yves-Marie Pers,&nbsp;Céline Michel,&nbsp;Marion Lepelley,&nbsp;Marie-Blanche Valnet-Rabier,&nbsp;Jean-Luc Faillie,&nbsp;Virginie Bres,&nbsp;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}

{"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 &amp; 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 ^{\u0000 <b>1</b>\u0000}\u0000 <b>, Buse Kose Demirezen</b>\u0000 ^{\u0000 <b>2</b>\u0000}\u0000 <b>, Arzu Yay</b>\u0000 ^{\u0000 <b>3</b>\u0000}\u0000 <b>, Ozge Cengiz Mat</b>\u0000 ^{\u0000 <b>4</b>\u0000}\u0000 <b>, Mustafa Ermis</b>\u0000 ^{\u0000 <b>5</b>\u0000}\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}

{"title":"French-Speaking Network of Pharmacogenetics (RNPGx) Recommendations for Gene Panel Analysis Through Genotyping or Sequencing in Pharmacogenetics","authors":"Nicolas Picard,&nbsp;Estelle Ayme-Dietrich,&nbsp;Sylvie Quaranta,&nbsp;Tiphaine Adam-De-Beaumais,&nbsp;Abd El Kader Ait Tayeb,&nbsp;Hugo Alarcan,&nbsp;Dorra Amor,&nbsp;David Barthelemy,&nbsp;Mouna Ben Sassi,&nbsp;Séverine Cunat,&nbsp;Mouna Daldoul,&nbsp;Hervé Delacour,&nbsp;Marie-Christine Etienne-Grimaldi,&nbsp;Xavier Fonrose,&nbsp;Benjamin Hennart,&nbsp;Louis Lebreton,&nbsp;Stephanie Malard,&nbsp;Céline Narjoz,&nbsp;Asma Omezzine,&nbsp;Nicolas Pallet,&nbsp;Léa Payen,&nbsp;Jeanne Petit,&nbsp;Fabienne Thomas,&nbsp;Sameh Trabelsi,&nbsp;Camille Tron,&nbsp;Céline Verstuyft,&nbsp;Paul Vilquin,&nbsp;Jean-Christophe Boyer,&nbsp;Vincent Haufroid,&nbsp;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}

{"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}

{"title":"Use of Psychoactive Substances Before Incarceration Among Prison Inmates With Drug Abuse or Dependence: Data From the OPPIDUM Program","authors":"Zeinab Abbas,&nbsp;Clémence Lacroix,&nbsp;Elisabeth Jouve,&nbsp;Céline Eiden,&nbsp;Joelle Micallef,&nbsp;Hélène Peyrière,&nbsp;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> &lt; 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}