Fundamental & Clinical Pharmacology最新文献

{"title":"Safety of Proton Pump Inhibitor in Paediatrics: A Study Based on EudraVigilance Data","authors":"Greta Santi Laurini,&nbsp;Victoria Nikitina,&nbsp;Nicola Montanaro,&nbsp;Domenico Motola","doi":"10.1111/fcp.70036","DOIUrl":"https://doi.org/10.1111/fcp.70036","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Objectives</h3>\u0000 \u0000 <p>Despite limited paediatric approvals, the use of proton pump inhibitors (PPIs) among children has increased in recent years, and concerns have arisen about their safety, including the risk of allergies. To provide additional evidence on the paediatric safety of PPIs, we performed a study on suspected adverse drug reactions (ADRs) in clinical practice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We retrieved from EudraVigilance reports of suspected ADRs for PPIs in the age class 0–11 years in the period 2003–2022. Most reported ADRs and allergic conditions were evaluated by descriptive analysis. A case-non-case analysis was performed using reporting odds ratio (ROR) with a 95% confidence interval (CI). Chi-square or Fisher's exact tests were used to detect differences in reporting rates.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 1389 reports and 4157 suspected ADRs were analysed. Most reports involved omeprazole (46.9%) and esomeprazole (27.3%), and 75.8% concerned serious outcomes. Gastrointestinal disorders were among the most common suspected ADRs, with vomiting being the most frequently reported (2.3%). Among allergic conditions, there were six cases of toxic epidermal necrolysis, five of Stevens–Johnson syndrome and four of drug reaction with eosinophilia and systemic symptoms. Statistically significant reactions for omeprazole were choking (ROR 5.54; 95% CI, 1.04–29.56) and pneumonia (3.61; 1.41–9.20), while for esomeprazole gastrointestinal disorder (7.57; 1.18–48.60) and constipation (4.74; 2.25–9.98).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Most common suspected ADRs reported with paediatric PPI use in Europe were gastrointestinal disorders, consistent with the safety profile in the product license. However, a high proportion of serious ADRs and few cases of severe cutaneous adverse reactions were reported.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"39 4","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/fcp.70036","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144573289","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":"DPD Ultra-Rapid Metabolizer Status and Efficacy of 5-Fluorouracil Treatment: A Real-World Study","authors":"Govind Kallee,&nbsp;Gérard Milano,&nbsp;Florence Duffaud,&nbsp;Laetitia Dahan,&nbsp;Joseph Ciccolini","doi":"10.1111/fcp.70035","DOIUrl":"https://doi.org/10.1111/fcp.70035","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Anticancer drug 5FU is extensively metabolized by dihydropyrimidine dehydrogenase (DPD), an enzyme with high interindividual variability. Poor metabolizer (PM, i.e., DPD deficient) patients are at risk of life-threatening toxicities. Whether ultra-rapid metabolizer (UM) status could conversely compromise 5FU efficacy remains to be investigated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this real-world study, 352 adult patients treated with a 5FU-containing regimen were screened. Patients were classified as normal (extensive metabolizer, EM), PM, or UM on DPD function based upon baseline plasma uracil monitoring. The impact of DPD status on efficacy and safety endpoints was investigated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patients were categorized on DPD as UM (11.9%), EM (75.9%), and PM (12.2%). The response rate was 54.5%, with median PFS and OS of 13.9 and 19 months, respectively. PM patients were treated with an average 13% lower 5FU starting dose. There was no statistical difference in efficacy between UM and other patients. Severe toxicities were observed in less than 5% of patients, an incidence significantly lower than commonly reported with 5FU-containing regimen and was comparable between UM, EM, and PM patients. Our observations suggest that UM status is not associated with the lack of efficacy of 5FU. In addition, upfront DPD testing with adaptive dosing helps to reduce the incidence of severe toxicities, as PM patients on reduced doses did not have more severe toxicities than other patients treated with standard doses, while exhibiting similar efficacy in terms of response rate and survival.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>When upfront DPD screening with adaptive dosing is performed, no difference is observed between UM, EM, and PM patients in terms of efficacy and safety.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>#PADSA3GKW7</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"39 4","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/fcp.70035","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144573288","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":"Effects of FECH Gene Polymorphisms and Serum Ferrochelatase Levels on Antituberculosis Drug-Induced Liver Injury in China","authors":"Jingru Cheng,&nbsp;Nannan Wang,&nbsp;Ruina Chen,&nbsp;Hongqiu Pan,&nbsp;Lihuan Lu,&nbsp;Meiling Zhang,&nbsp;Xiaomin He,&nbsp;Honggang Yi,&nbsp;Shaowen Tang","doi":"10.1111/fcp.70034","DOIUrl":"https://doi.org/10.1111/fcp.70034","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>The pathogenic mechanism of antituberculosis drug-induced liver injury (ATLI) has not been elucidated. This study aimed to investigate the effects of FECH genetic polymorphisms and serum ferrochelatase levels on ATLI in the Chinese population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>One case–control study was conducted to investigate the association between four SNPs in FECH gene and ATLI, while another was used to analyze the association of serum ferrochelatase levels at three different times with ATLI. Multivariate logistic regression model was used to screen potential risk factors for ATLI, and the results were expressed as odds ratios (ORs) with 95% confidence intervals (CIs). The area under receiver operating characteristic curve (AUC) was calculated to estimate the performance for distinguishing ATLI cases from controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Serum ferrochelatase levels were lower in ATLI cases than in controls at the time of baseline test, the first test and the second test after initial treatment. A multivariate logistic regression model showed that SNP rs536560 in the FECH gene (OR = 2.063, 95%CI: 1.112–3.892, <i>p</i> = 0.023), baseline serum ferrochelatase level (OR = 3.162, 95%CI: 1.605–6.234, <i>p</i> = 0.001), and liver disease history (OR = 2.915, 95%CI: 1.301–6.461, <i>p</i> = 0.008) were the risk factors for ATLI. The ROC curves demonstrated that the model including the above three factors has strong discriminating ability (AUC = 0.709, 95%CI: 0.639–0.779, <i>p</i> &lt; 0.0001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study is the first to explore the relationships between SNPs in the FECH gene, serum ferrochelatase levels, and ATLI in China, and SNP rs536560 in the FECH gene, baseline ferrochelatase level, and liver disease history may be associated with susceptibility to ATLI.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"39 4","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144514637","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":"Differential Effects of Prenatal Poly I:C Exposure and Antipsychotics on NMDA/GABA Receptors and GSK3β-Mediated Signaling in the Dorsal Raphe Nucleus of Female Rats","authors":"Shiyan Chen,&nbsp;Jiamei Lian,&nbsp;Yueqing Su,&nbsp;Chao Deng","doi":"10.1111/fcp.70033","DOIUrl":"https://doi.org/10.1111/fcp.70033","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The dorsal raphe nucleus (DRN) is the origin of the 5-HT neurotransmission pathways. The 5-HT, dopamine D2, GABA, and NMDA receptors, as well as the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) and G protein-independent protein kinase B (PKB/Akt)-glycogen synthase kinase 3β (GSK3β) signaling, are involved in the pathophysiology of schizophrenia and are modulated by antipsychotics. However, their pathological changes and antipsychotic modulations in the DRN are not well understood in schizophrenia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>This study explored effects of antipsychotics on NMDA and GABA_A receptors, as well as PKA, AKT-GSK3β, cAMP-responsive element-binding protein 1 (CREB1), and disheveled (Dvl)-β-catenin signaling in the DRN using a maternal immune activation rat model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Prenatal polyriboinosinic-polyribocytidylic acid (Poly I:C) exposure was delivered at gestational Day 15. Female rats were treated with risperidone, olanzapine, or vehicle from postnatal day 70 for 35 days.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Prenatal Poly I:C exposure increased mRNA expression of NMDA receptor <i>Grin2a/2b</i> subunits, the GABA_A receptor <i>β3</i> subunit, glutamic acid decarboxylase 1 (<i>GAD1</i>), <i>AKT1/3</i>, and <i>GSK3β</i> in the DRN. Antipsychotics significantly increased the mRNA expression of <i>PKA</i>, <i>CREB1</i>, <i>β-catenin</i>, <i>GSK3β</i>, and <i>Grin2d</i> subunits in the DRN of Poly I:C rats. Prenatal Poly I:C exposure led to decreased expression of <i>GAD2</i>, which was partially reversed antipsychotics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study suggests that prenatal Poly I:C exposure and antipsychotics differentially modulate NMDA and GABA_A receptors, as well as AKT-GSK3β, PKA-CREB1, and Dvl-β-catenin signaling in the DRN of rats. Poly I:C mainly influenced the AKT-GSK3β signaling, while antipsychotics modulated the AKT-GSK3β, PKA-CREB1, and Dvl-GSK3β-β-catenin signaling pathways in the DRN.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"39 4","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/fcp.70033","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482051","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":"Master 2 award","authors":"","doi":"10.1111/fcp.70019","DOIUrl":"https://doi.org/10.1111/fcp.70019","url":null,"abstract":"","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"39 S1","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339391","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":"Discussed poster abstracts—PM2","authors":"","doi":"10.1111/fcp.70022","DOIUrl":"https://doi.org/10.1111/fcp.70022","url":null,"abstract":"","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"39 S1","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339394","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":"Drug news and therapeutic news","authors":"","doi":"10.1111/fcp.70017","DOIUrl":"https://doi.org/10.1111/fcp.70017","url":null,"abstract":"","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"39 S1","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339557","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":"Oral communication abstracts","authors":"","doi":"10.1111/fcp.70018","DOIUrl":"https://doi.org/10.1111/fcp.70018","url":null,"abstract":"","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"39 S1","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339390","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":"Thesis awards","authors":"","doi":"10.1111/fcp.70020","DOIUrl":"https://doi.org/10.1111/fcp.70020","url":null,"abstract":"","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"39 S1","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339392","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":"Discussed poster abstracts—PM1","authors":"","doi":"10.1111/fcp.70021","DOIUrl":"https://doi.org/10.1111/fcp.70021","url":null,"abstract":"","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"39 S1","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339393","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}