British journal of clinical pharmacology最新文献

{"title":"Use of cimetidine to enhance systemic acyclovir concentrations in patients with ineffective suppressive therapy for recurring herpes simplex virus infections: A novel purpose for an old drug.","authors":"Dominique G Stuijt, Victor M Cnossen, Amira F Y S M Osman, Teun van Gelder, Sandra M Arend","doi":"10.1111/bcp.70313","DOIUrl":"https://doi.org/10.1111/bcp.70313","url":null,"abstract":"<p><p>Herpes simplex virus (HSV) may cause recurring oral or genital ulcers. We report a series of patients nonresponsive to suppressive valacyclovir therapy, explained by subtherapeutic acyclovir plasma levels. After a dose increase, or in some patients only after concomitant prescription of cimetidine, adequate levels were reached associated with significant clinical improvement.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age-related differences in hydroxychloroquine-associated adverse events: A pharmacovigilance study based on the FDA Adverse Event Reporting System.","authors":"Guanghan Sun, Jingrong Yang, Lei Wan, Xia Xu, Jing Wang","doi":"10.1002/bcp.70293","DOIUrl":"https://doi.org/10.1002/bcp.70293","url":null,"abstract":"<p><strong>Aims: </strong>This real-world pharmacovigilance study utilizes FDA Adverse Event Reporting System (FAERS) data (2004-2024) to characterize age-related disparities in hydroxychloroquine (HCQ)-associated adverse events (AEs), addressing gaps in age-stratified risk assessment.</p><p><strong>Methods: </strong>Disproportionality analysis (reporting odds ratios, RORs) and parametric Weibull modelling were applied to compare AE signals and time-to-onset profiles between paediatric (≤18 years; n = 1744) and geriatric (≥60 years; n = 14 115) populations from 22 249 476 HCQ-related reports.</p><p><strong>Results: </strong>Paediatric AEs exhibited significantly earlier onset (median 9.5 days vs. 19 days). Ten novel paediatric-specific signals were identified, including COVID-19-related cardiotoxicity (ROR = 3.26, 95% confidence interval [CI] 1.87-6.94) and hypokalaemia complications (ROR = 25.77, 95% CI 18.7-35.52), with distinct reporting patterns compared to geriatric cohorts. Weibull shape parameters revealed divergent risk trajectories: constant hazard profiles in children (α = 0.52, β = 46.68) contrasted with escalating risks in older adults (α = 0.40, β = 93.66), suggesting mechanistic differences in toxicity progression.</p><p><strong>Conclusions: </strong>Significant age-related variations in HCQ-associated AE profiles, temporal dynamics and risk evolution underscore the necessity for age-stratified pharmacovigilance frameworks. Paediatric-specific cardiotoxic and metabolic risks, coupled with geriatric-specific cumulative toxicity patterns, mandate tailored therapeutic monitoring strategies to optimize safety across age extremes.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145257414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing mycophenolic acid exposure for reduced relapse risk in paediatric nephrotic syndrome: An observational cohort study.","authors":"Yiting Cai, Baojing Liu, Lizhi Chen, Lu Zhang, Kejing Tang, Xiaoyun Jiang, Pan Chen","doi":"10.1002/bcp.70307","DOIUrl":"https://doi.org/10.1002/bcp.70307","url":null,"abstract":"<p><strong>Aims: </strong>Mycophenolic acid (MPA) effectively reduces relapse in paediatric nephrotic syndrome (NS), yet its pharmacokinetic variability hinders optimal dosing. This study aimed to define risk reference values of MPA area under the concentration-time curve (AUC_0-12h) for relapse prevention during maintenance therapy.</p><p><strong>Methods: </strong>In this retrospective cohort study, 89 paediatric NS patients receiving MPA were enrolled. Factors influencing relapse were evaluated via binary logistic regression. Optimal cut-off threshold were determined using receiver operating characteristic (ROC) curves, while Kaplan-Meier and Cox regression analyses assessed relapse-free survival (RFS).</p><p><strong>Results: </strong>Lower MPA AUC_0-12h levels strongly correlated with relapse (relapse group: 31.49 vs. non-relapse: 36.48 μg/h/mL, P < 0.001). Logistic regression confirmed MPA AUC_0-12h as a protective factor (odds ratio [OR] = 0.93, 95% confidence interval [CI]: 0.88-0.99). ROC analysis identified 31.51 μg/h/mL as the optimal risk reference value (sensitivity = 87.5%, specificity = 51.02%). Cox regression further demonstrated subthreshold exposure as an independent relapse risk (hazard ratio [HR] = 0.24, 95% CI: 0.14-0.43, P < 0.001). Subgroup analyses validated this risk reference value across corticosteroid response, relapse frequency and rituximab use, though not in focal segmental glomerulosclerosis.</p><p><strong>Conclusions: </strong>Maintaining MPA AUC_0-12h ≥ 31.51 μg/h/mL significantly reduces relapse risk in paediatric NS. Individualized mycophenolate mofetil (MMF) dosing guided by therapeutic drug monitoring is critical for optimizing outcomes.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetic profiles of sertraline in pregnancy as a predictor of postpartum depressive symptoms.","authors":"Sílvia M Illamola, Zachary N Stowe, Marc L Kalin, Michael D Evans, Catherine M Sherwin, Maged M Costantine, D Jeffrey Newport, James C Ritchie, Angela K Birnbaum","doi":"10.1002/bcp.70283","DOIUrl":"https://doi.org/10.1002/bcp.70283","url":null,"abstract":"<p><strong>Aim: </strong>To characterize pharmacokinetic changes of sertraline and its metabolite during pregnancy and postpartum, and their relationship to maternal postpartum depressive symptoms.</p><p><strong>Methods: </strong>This was a prospective observational, longitudinal study of pregnant women with a major depressive disorder treated with sertraline (N = 185 women, 205 pregnancies). Women were enrolled at <16 weeks' gestation and followed at 4-8 week intervals throughout pregnancy and the first postpartum year. Baseline measures included structured clinical interviews and demographic information. Drug and metabolite concentrations and psychometric measures (study outcomes) (ie, Hamilton Rating Scale for depression - 17 item, Beck Depression Inventory, Edinburgh Postnatal Depression Scale [EPDS], Clinical Global Impression [CGI]) were measured at follow-up visits. Serum sertraline and N-desmethylsertraline exposure were reported asstandardized 24-h concentration-to-dose (C/D) and parent to metabolite (P/M) ratios. Linear mixed-effects and latent trajectory models were used to characterize longitudinal patterns in concentration measures across pregnancy and postpartum, and their association with study outcomes.</p><p><strong>Results: </strong>Mean 24-h C/D ratios showed high variability throughout pregnancy and postpartum that were characterized by three trajectories for sertraline and five for N-desmethylsertraline and P/M ratio corresponding to different sertraline pharmacokinetic profiles. At postpartum, sertraline drug exposure was inversely associated with higher EPDS score (P < .05), while N-desmethylsertraline exposure was associated with higher scores for all measured depression scales (P < .001). Higher P/M ratios had higher CGI scores (P < .05) postpartum.</p><p><strong>Conclusion: </strong>Sertraline pharmacokinetic profiles varied across pregnant women and were associated with postpartum depressive symptoms. The use of therapeutic monitoring may provide clinical insight that can be useful for identifying patients with a potential toward depressive symptoms.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145243778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Population pharmacokinetics of artemether-lumefantrine plus amodiaquine in patients with uncomplicated Plasmodium falciparum malaria.","authors":"Junjie Ding, Richard M Hoglund, Rob W van der Pluijm, James J Callery, Thomas J Peto, Rupam Tripura, Sukanta Das, Nguyễn Hoàng Châu, Cholrawee Promnarate, Mavuto Mukaka, Lek Dysoley, Caterina Fanello, Marie A Onyamboko, Anupkumar R Anvikar, Mayfong Mayxay, Frank Smithuis, Lorenz von Seidlein, Mehul Dhorda, Chanaki Amaratunga, M Abul Faiz, Ho Dang Trung Nghia, Nicholas J White, Nicholas P J Day, Arjen M Dondorp, Joel Tarning","doi":"10.1002/bcp.70301","DOIUrl":"https://doi.org/10.1002/bcp.70301","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Aims: &lt;/strong&gt;Resistance to the artemisinins and the artemisinin-based combination therapy (ACT) partner drugs has developed in Southeast Asia, and artemisinin resistance has also emerged in eastern Africa. Triple ACTs (triple artemisinin-based combination therapies, TACT), consisting of two partner drugs with different mechanisms of action and similar pharmacokinetic profiles, combined with an artemisinin derivative can help to delay or prevent artemisinin resistance and prolong the useful lifetime of the partner drugs. This study aims to characterize the pharmacokinetic properties of a recommended TACT, artemether-lumefantrine plus amodiaquine, using data from two large clinical trials.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We analysed data from two randomized, controlled intervention trials conducted between 2015 and 2020 in one African country and two Southeast Asian countries, in which artemether-lumefantrine was administered alone (n = 443) or together with amodiaquine (n = 442) to patients with uncomplicated P. falciparum malaria. Both studies included a sub-cohort with dense pharmacokinetic sampling, combined with sparse data in the other patients. Concentration-time data of artemether, dihydroartemisinin, lumefantrine, desbutyllumefantrine, amodiaquine and desethylamodiaquine were analysed using nonlinear mixed-effects modelling.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Pharmacokinetic models were developed for all drugs and demonstrated good predictive performance and goodness-of-fit diagnostics. Coadministered amodiaquine was not a significant covariate on pharmacokinetic properties of artemether-lumefantrine. Model-predicted C&lt;sub&gt;max&lt;/sub&gt; and AUC (median [95% confidence interval, CI]) for artemether were 256 (159-407) ng/mL and 2850 (1820-4920) h·ng/mL for artemether-lumefantrine alone, and 230 (123-391) ng/mL and 2800 (1570-4570) h·ng/mL for artemether-lumefantrine-amodiaquine. For dihydroartemisinin, values were 135 (54.5-214) ng/mL and 1870 (813-3015) h·ng/mL for artemether-lumefantrine alone, and 116 (40.8-186) ng/mL and 1580 (547-2680) h·ng/mL for artemether-lumefantrine-amodiaquine. For lumefantrine, values were 15.2 (2.90-31.3) μg/mL and 600 (275-1230) h·μg/mL for artemether-lumefantrine alone, and 14.1 (2.72-31.4) μg/mL and 586 (269-1070) h·μg/mL for artemether-lumefantrine-amodiaquine. Day 7 concentrations of lumefantrine were 452 (215-1240) and 438 (204-1030) μg/mL for artemether-lumefantrine alone and artemether-lumefantrine-amodiaquine, respectively. All geometric mean ratios (GMRs) for the drug-drug interaction (DDI) effect on key pharmacokinetic parameters of artemether, dihydroartemisinin and lumefantrine fell within the 0.80-1.25 range, with the majority of the corresponding 90% CI also contained within this range. This indicates no clinically relevant DDIs between artemether-lumefantrine and amodiaquine.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;The DDI effect of amodiaquine on the pharmacokinetics of artemether-lumefantrine","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the Medicines and Healthcare products Regulatory Agency's introduction of a risk-proportionate approach for clinical trials: An analysis of 4617 applications assessed between September 2023 and August 2024.","authors":"Andrea Manfrin, Kingyin Lee, Crina Cacou, James Pound, Anthony Harnden, June Raine, Munir Pirmohamed","doi":"10.1002/bcp.70308","DOIUrl":"https://doi.org/10.1002/bcp.70308","url":null,"abstract":"<p><strong>Aims: </strong>The Medicines and Healthcare products Regulatory Agency (MHRA) introduced a risk-proportionate approach to assess clinical trial applications for authorisation in August 2023. This study evaluates the impact of this approach on the timelines for reviewing proposals.</p><p><strong>Methods: </strong>Data on new clinical trial initial submissions and substantial amendments were extracted from the MHRA's clinical trials unit database. The primary endpoint was the number of days for the MHRA's first review of initial applications. The secondary endpoints were the days taken by the sponsor's replies to grounds for nonacceptance, the MHRA's days to issue the final decision and the percentage of reviews within statutory timelines. For substantial amendments, the days for the final decision and the percentage of statutory timelines met were the endpoints.</p><p><strong>Results: </strong>Between September 2023 and August 2024, 4617 applications were received, 615 relating to initial clinical trial submissions, while 4002 were substantial amendments. The first review was completed within the statutory timelines for 99% of submissions, with a median of 28 days (interquartile range [IQR] 27-30); 48.5% of sponsors' replies to grounds for nonacceptance met the statutory timelines with no statistically significant difference between the commercial and noncommercial sponsors (median 15 days, IQR 9-22). The final decision from the MHRA was within the nonstatutory timelines (median 15 days, IQR 13-27); 99.9% of the substantial amendments were completed within the statutory timelines (median 31 days, IQR 24-34).</p><p><strong>Conclusion: </strong>The MHRA's risk-proportionate approach enabled the Clinical Trials Unit to consistently meet its timelines, confirming its reliability, consistency and predictability while maintaining its priority to protect patient safety.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neck-vein thrombosis during spaceflight.","authors":"Ulrich Limper, Jens Jordan","doi":"10.1002/bcp.70300","DOIUrl":"https://doi.org/10.1002/bcp.70300","url":null,"abstract":"<p><p>Spaceflight imposes unique environmental challenges, including weightlessness, increased radiation exposure and confinement, which can lead to unexpected health effects. One such example is neck-vein thrombosis, a condition rarely seen on Earth without predisposing factors such as venous catheters or infections. Although spaceflight has not previously been associated with thromboembolic events, recent cases of neck-vein thrombosis in astronauts aboard the International Space Station have raised concern. These events were detected incidentally and showed no obvious symptoms, complicating diagnosis. Retrospective studies have not found consistent biomarkers indicating a hypercoagulable state in space, but environmental factors such as weightlessness-induced venous stasis and potential endothelial damage may contribute. Oral contraceptives could promote thrombotic risk in female astronauts, although no direct link has been confirmed. Research on terrestrial models simulating space conditions has not yet provided conclusive insights into thrombosis prevention. Given the challenges in diagnosing and treating thrombosis in space, agencies such as National Aeronautics and Space Administration and European Space Agency have implemented surveillance programmes and recommended risk-mitigation strategies, including careful management of venous flow abnormalities and cautious use of anticoagulants. However, more research is needed to refine these strategies and improve safety in future deep space missions.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between use of lubiprostone and headache: A systematic review and meta-analysis of randomized controlled trials.","authors":"Satoru Mitsuboshi, Makoto Morizumi, Shungo Imai, Satoko Hori, Kazumasa Kotake","doi":"10.1002/bcp.70305","DOIUrl":"https://doi.org/10.1002/bcp.70305","url":null,"abstract":"<p><strong>Aims: </strong>Lubiprostone and its active metabolite may activate prostaglandin receptors, raising concerns about an increased risk of headache. We performed a systematic review and meta-analysis to identify whether lubiprostone increases the risk of headache.</p><p><strong>Methods: </strong>To identify all relevant randomized controlled trials (RCTs), we comprehensively searched MEDLINE (via PubMed), ClinicalTrials.gov website and the Cochrane Central Register of Controlled Trials. The search focused on studies comparing lubiprostone vs. placebo or other laxatives. A DerSimonian-Laird random-effects model was utilized to estimate risk ratios (RRs) and 95% confidence intervals (CIs). A fixed-effect method based on the Mantel-Haenszel method was employed for analyses with 3 or fewer studies. Heterogeneity was assessed using the I² statistic, and the certainty of evidence was rated using the GRADE approach.</p><p><strong>Results: </strong>Twenty-six studies were examined in the analysis. The incidence of headache was 5.3% for lubiprostone and 3.2% for placebo or other laxatives. Lubiprostone increased the risk of headache (RR 1.32, 95% CI 1.02-1.71, I² = 0%, 6265 patients, 26 RCTs, moderate certainty) relative to placebo or other laxatives. The risk of headache seemed to be consistently increased in both adults (RR 1.23, 95% CI 0.93-1.62, I² = 0%, 5390 patients, 24 RCTs, moderate certainty) and children (RR 3.07, 95% CI 1.67-5.63, I² = 84.4%, 875 patients, 2 RCTs, very low certainty).</p><p><strong>Conclusion: </strong>The results of this meta-analysis suggest that lubiprostone treatment increases the risk of headache in adults.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Budget impact analysis of new drugs in oncology and haematology: Principles and practice.","authors":"Javier Soto-Alsar, José L Revuelta-Herrero, Cristina Villanueva-Bueno, Carmen Cobos-Lama, Marc A Cañete-Muñoz, Andrés Muñoz-Martín, Pilar García-Alfonso, Javier Soto-Álvarez","doi":"10.1002/bcp.70303","DOIUrl":"https://doi.org/10.1002/bcp.70303","url":null,"abstract":"<p><p>Cancer is currently among the most prevalent and fatal diseases, so new, costly drugs for its treatment will be available in the coming years. Budget impact analyses (BIAs) are an essential component of the economic evaluation of new oncological and haematological drugs, and are increasingly required by health authorities in many countries as part of the pricing and reimbursement process. This article aims to provide updated guidance on the methodology for performing such analyses. In a BIA, the resource consumption in the reference scenario (before the new drug is introduced) is always compared with the resource consumption in the future scenario (after the new treatment is commercialized). The most important parts of a BIA include calculating the number of the existing patient population, the current mix of treatments and the expected mix after the coming of the new drug, the cost of the treatment mixes and other changes in cancer-related costs. The BIA's data sources should be drawn from the best available published evidence, such as clinical trials, observational studies, local epidemiological information, cost databases and expert opinion. Where possible, the decision maker's population and calculations for other parameter estimations should also be included. A deterministic analysis and a scenario sensitivity analysis should be carried out in every BIA. The BIA report must provide details of resource consumption and associated costs in the reference scenario and the future scenario. The difference between the 2 scenarios will represent the budget impact of introducing a new drug to the market.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of empagliflozin for treating neutropenia and neutrophil dysfunction in paediatric patients with glycogen storage disease type Ib: A systematic review and meta-analysis.","authors":"Elizabeth Iwasyk, Ryan Jin, Fabio Tuzzolino, Giusy Ranucci, Donatella Madonia, Alessio Provenzani","doi":"10.1002/bcp.70294","DOIUrl":"https://doi.org/10.1002/bcp.70294","url":null,"abstract":"<p><strong>Aims: </strong>Glycogen storage disease type Ib (GSD-Ib) is a rare genetic disorder causing neutropenia and neutrophil dysfunction in children. G-CSF has been the primary treatment, but emerging data support the potential of empagliflozin, an SGLT2 inhibitor, as a promising investigational option. This systematic review and meta-analysis assess its feasibility, efficacy and safety in paediatric GSD-Ib patients.</p><p><strong>Methods: </strong>Following the 2020 PRISMA guidelines, a systematic search was conducted in PubMed, Embase and Web of Science (2015-2025). The last search was performed on 16 May 2025. The inclusion criteria were patients <18 years with GSD-Ib and neutropenia treated with empagliflozin. Eligible study types included randomized controlled trials (RCTs), observational studies and case series. Non-English, pre-2015 and non-primary research were excluded. Bias was assessed using ROBINS-I V2, and certainty via GRADE. Meta-analyses used fixed or random effects depending on heterogeneity. The primary efficacy outcome was defined as resolution of neutropenia, and safety outcome included overall adverse events.</p><p><strong>Results: </strong>Six non-randomized studies (n = 177; 52% male; mean age 6.7) met the inclusion criteria. Two studies showed low risk of bias; three were critically biased. All reported improved neutrophil counts (ANC > 1.5) after empagliflozin treatment. Four studies had >80% resolution of neutropenia; all showed G-CSF reduction or discontinuation. Adverse events were minimal; lactic acidosis was the most serious.</p><p><strong>Conclusions: </strong>Empagliflozin shows promise in treating neutropenia in paediatric GSD-Ib patients, with encouraging efficacy and safety. However, findings are limited by study design and heterogeneity. The majority of included studies were non-randomized and rated as having a serious or critical risk of bias according to the ROBINS-I tool. This substantially limits the reliability and interpretability of pooled outcomes. These results should therefore be viewed as preliminary and interpreted with caution. Further randomized trials, especially those measuring 1,5-AG, are needed to confirm empagliflozin's role as promising therapy in G-CSF.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}