British journal of clinical pharmacology最新文献

{"title":"Cardiovascular and neuroendocrine dynamics in antibiotic dose individualization in intensive care.","authors":"Mehmet Ertugrul Balkar","doi":"10.1002/bcp.70688","DOIUrl":"10.1002/bcp.70688","url":null,"abstract":"","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":"3694-3695"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148403533","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":"Predicting cognitive function in Alzheimer's clinical trials via amyloid β-protein biomarkers.","authors":"Zichao Sui, Aobo Feng, Yiwen Gong, Sijie Zha, Yinghua Lv, Qingshan Zheng, Lujin Li, Yaning Wang","doi":"10.1002/bcp.70665","DOIUrl":"10.1002/bcp.70665","url":null,"abstract":"<p><strong>Objectives: </strong>This study investigates the association between amyloid-β (Aβ) biomarkers and clinical cognitive outcomes and quantitatively elucidates their relationship, providing robust evidence supporting the amyloid hypothesis and advancing the development of novel anti-amyloid therapeutics, such as aducanumab, lecanemab and donanemab.</p><p><strong>Methods: </strong>Placebo-controlled randomized clinical trials reporting Aβ-related biomarkers and cognitive function clinical outcomes were retrieved from PubMed, EMBASE and Cochrane Library. Pearson correlation analysis was first used to screen indices, and then a model-based meta-analysis (MBMA) using non-linear mixed-effect modelling was established to predict cognitive function based on biomarkers while examining relevant factors affecting the relationship.</p><p><strong>Results: </strong>Primary outcomes included changes in the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) and the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-COG-11). The analysis included 57 articles representing 93 417 subjects, with a modelling subset of 18 246 patients providing paired biomarker-endpoint data for Alzheimer's disease or mild cognitive impairment. Results showed significant correlations between the standard uptake value ratio (SUVR) of β-amyloid plaques and CDR-SB, centiloid and CDR-SB, and SUVR and ADAS-COG-11. Three prediction models of cognitive function scales based on imaging index of β-amyloid plaques were established and found to be significantly impacted by factors such as baseline CDR-SB, treatment duration and the proportion of patients receiving basic treatment.</p><p><strong>Conclusions: </strong>This study clarified the correlation and established predictive models for CDR-SB and ADAS-COG-11 based on amyloid imaging. This research identifies potential biomarkers and model-derived benchmarks for future dose selection and decision-making in Alzheimer's drug development, potentially accelerating the development of new treatments.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":"3576-3585"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148343885","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":"Comment on 'Multifactorial attribution for vancomycin-associated acute kidney injury'.","authors":"Wenbo Hu, Menglu Ni, Jian Kang","doi":"10.1002/bcp.70681","DOIUrl":"https://doi.org/10.1002/bcp.70681","url":null,"abstract":"","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104298","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":"The effect of mild and moderate hepatic impairment on the pharmacokinetics, safety and tolerability of balcinrenone.","authors":"Anna L Eriksson, Deeyen Karsanji, Bonifride Tuyishimire, Joanna Parkinson, Maria Heijer, Tadeusz Pawlik, Judith Hartleib-Geschwindner, Maria Leonsson-Zachrisson, Hans Ericsson","doi":"10.1002/bcp.70670","DOIUrl":"10.1002/bcp.70670","url":null,"abstract":"<p><strong>Aim: </strong>Balcinrenone (previously AZD9977) is a novel selective non-steroidal mineralocorticoid receptor antagonist (MRA) with a differential mechanism of action relative to approved MRAs. The aim of this trial was to assess the pharmacokinetics, safety and tolerability of balcinrenone in participants with mild and moderate hepatic impairment versus participants with normal hepatic function.</p><p><strong>Methods: </strong>Participants with mild and moderate hepatic impairment (Child-Pugh Class A [n = 8] and Child-Pugh Class B [n = 8]) were compared with group matched controls with normal hepatic function [n = 9]. Eligible participants received a single oral dose of 50-mg balcinrenone. Blood and urine samples were collected. Safety and tolerability were monitored.</p><p><strong>Results: </strong>In participants with mild hepatic impairment, balcinrenone exposure (area under the plasma concentration-time curve [AUC] and maximum plasma concentration [C_max]) was similar compared with participants with normal hepatic function. In participants with moderate hepatic impairment, C_max was similar, but there was a slight and statistically significant 30% (90% CI 4%-61%) increase in AUC compared with participants with normal hepatic function. Balcinrenone was well tolerated. All reported adverse events were of mild to moderate intensity.</p><p><strong>Conclusions: </strong>Compared with participants with normal hepatic function, balcinrenone exposure was similar in participants with mild hepatic impairment. AUC, but not C_max, was slightly increased in participants with moderate hepatic impairment. We do not consider the minor AUC increase seen in participants with moderate hepatic impairment to be clinically relevant. Thus, we would not recommend any dose adjustment for patients with mild or moderate hepatic impairment.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":"3656-3665"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13619022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148374676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of esomeprazole on the pharmacokinetics of vepdegestrant, a PROteolysis TArgeting Chimera oestrogen receptor degrader, in healthy participants.","authors":"Lana Tran, Naihan Chen, Jennifer A Winton, Kyle T Matschke, Smita P Goodman, Kimberly C Lee, Yuanyuan Zhang, Weiwei Tan","doi":"10.1002/bcp.70636","DOIUrl":"10.1002/bcp.70636","url":null,"abstract":"<p><strong>Aims: </strong>The aim of this study is to evaluate the effects of multiple doses of esomeprazole, a strong proton pump inhibitor and acid-reducing agent, on the pharmacokinetics and safety of vepdegestrant, a PROteolysis TArgeting Chimera oestrogen receptor degrader.</p><p><strong>Methods: </strong>This was a Phase 1, open-label, two-period, crossover, single-dose study in healthy adult participants. During Period 1, on Day 1, a single oral dose of vepdegestrant 200 mg was administered with a moderate-fat meal following overnight fasting. During Period 2, esomeprazole 40 mg was administered once daily on Days 1-5; a single dose of vepdegestrant 200 mg was given with a moderate-fat meal on Day 5 following esomeprazole 40 mg. Serial blood samples for vepdegestrant pharmacokinetics and safety laboratory analyses were collected predose and up to 168 h after vepdegestrant dosing in each period. Safety was monitored throughout the study.</p><p><strong>Results: </strong>Twelve participants were enrolled and treated. Following administration of vepdegestrant with (test) and without (reference) esomeprazole, test/reference ratios (90% CIs) of the adjusted geometric means for vepdegestrant area under the plasma concentration-time curve from time 0 to infinity and maximum plasma concentration were 83.73% (76.32, 91.86) and 74.11% (63.47, 86.52), respectively. Similar decreases in ARV-473 (vepdegestrant epimer) plasma exposure were observed. All 12 treatment-emergent adverse events experienced by seven participants were mild in severity.</p><p><strong>Conclusion: </strong>Coadministration of multiple daily doses of esomeprazole 40 mg with vepdegestrant 200 mg under fed conditions in healthy adult participants resulted in mild decreases in vepdegestrant plasma exposure. Vepdegestrant 200 mg was well tolerated in healthy adult participants.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":"3477-3484"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13619030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148270342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Do consumers and healthcare professionals report the same adverse event differently? A paired analysis of duplicate vaccine safety reports in Norway.","authors":"Tommy Emil Dzus, Johaina Sarrage, Hilde Samdal, François Montastruc, Elena Rocca","doi":"10.1002/bcp.70648","DOIUrl":"10.1002/bcp.70648","url":null,"abstract":"<p><strong>Aim: </strong>This study aimed to compare how Norwegian healthcare professionals (HCPs) and consumers reported the same adverse event (AE) following immunization with vaccines against COVID-19 during the COVID-19 pandemic. Specifically, we aimed to compare the extent to which HCPs and consumers reported information relevant for assessing the causal relationship between the AE and the suspected COVID-19 vaccine, with a particular focus on the type of unstructured information provided by each group.</p><p><strong>Methods: </strong>Verified duplicate pairs of AE reports following COVID-19 vaccination were extracted from the Norwegian Adverse Drug Reaction Registry. Free-text case narratives were analysed using thematic analysis to categorize types of unstructured information. A scoring system quantified completeness of causality-relevant information, with final scores categorized into levels of completeness. Time intervals from AE onset to reporting were also calculated.</p><p><strong>Results: </strong>Nineteen categories of unstructured information were identified. HCPs more often provided vaccine dose details, clinical observations, test results and causality reflections, while consumers more often described dietary supplements, life consequences and subjective AE explanations (p < .05). In 85% of 127 duplicate pairs, HCPs and consumers provided at least 50% complementary information in free-text narratives. Both groups provided similar levels of causality-relevant information (p = .774). HCPs reported earlier than consumers (p < .05).</p><p><strong>Conclusion: </strong>HCPs and consumers provided highly complementary unstructured information and comparable completeness for causality assessment. Collaboration between these groups should be encouraged, particularly in public health and clinical emergencies like epidemics and in situations of high uncertainty.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":"3559-3575"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13619059/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148343836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modelling immune gene expression profiles as pharmacodynamic endpoints of antileishmanial treatment.","authors":"Neal Alexander, Lina Giraldo-Parra, David E Rebellón-Sánchez, María Adelaida Gómez","doi":"10.1002/bcp.70675","DOIUrl":"10.1002/bcp.70675","url":null,"abstract":"<p><strong>Background: </strong>Cutaneous leishmaniasis (CL), a neglected infectious disease caused by the intracellular protozoan parasite Leishmania, affects over one million people annually. The type and magnitude of the inflammatory response elicited during infection lead to skin-specific immunopathology, resulting in the clinical manifestations of CL. Systemic antileishmanial drugs are the main control measure; however, these are highly toxic, of long duration, and difficult to access for affected populations. New drugs and optimized regimens are urgently needed. Despite the known participation of immune responses in the pathology of CL, preclinical drug evaluations target parasite elimination as the efficacy measure. This overlooks the potential of host immune responses to influence therapeutic success.</p><p><strong>Methods: </strong>In this study, we evaluated the performance of non-linear pharmacokinetic/pharmacodynamic (PK/PD) models in recreating the exposure-response relationships between plasma antimony (Sb) concentrations in CL patients treated with Glucantime (Sb^V as meglumine antimoniate) and the gene expression dynamics of pro-inflammatory mediators in peripheral blood mononuclear cells.</p><p><strong>Results: </strong>A one-compartment PK model, coupled to an indirect PD model with endogenous regulators, fitted the data well, explaining 80%-90% of the variance. Our results suggest a mechanism of drug-dependent immune gene regulation involving modulation of cell signalling and RNA stability in CL patients who have been cured after treatment.</p><p><strong>Conclusions: </strong>The model presented herein can be used for evaluating immune gene expression, alongside parasite kill, as PD endpoints of antileishmanials, both for new drug developments and in optimization of available drug regimens.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":"3666-3675"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13404081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148374665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Managing HIV in the extreme: Viral load and drug monitoring in a patient with BMI > 60 on long-acting cabotegravir/rilpivirine therapy.","authors":"Leah D Baker, Patricia Pecora Fulco","doi":"10.1002/bcp.70732","DOIUrl":"10.1002/bcp.70732","url":null,"abstract":"<p><p>This case describes the use of long-acting injectable (LA-I) cabotegravir/rilpirivine (CAB/RPV) therapy in a morbidly obese person (body mass index [BMI] = 62 kg m^-2) living with HIV without sustained viral load (VL) suppression after historic poor adherence to daily oral antiretroviral therapy. Increased BMI > 30 kg m^-2 is a known risk factor for VL rebound with CAB/RPV failures; thus, RPV therapeutic drug monitoring (TDM) was followed with regularly scheduled VL assessments. Based on TDM concentrations, monthly dose titration from standard CAB/RPV 400 mg/600 mg to 600 mg/900 mg increased trough concentrations with VL suppression (<200 copies mL^-1) maintained. TDM may be an additional tool in this population with high BMI values to optimize CAB/RPV dosing strategies as data accumulate in this high-risk group for viral rebound with LA-I therapy.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":"3687-3690"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148700894","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":"Applying machine learning to pharmacovigilance data: A proof-of-concept study.","authors":"Romain Barus, Pauline Schiro, Jean-Luc Faillie, Romane Freppel, Johana Béné, Claire de Canecaude, François Montastruc","doi":"10.1002/bcp.70655","DOIUrl":"10.1002/bcp.70655","url":null,"abstract":"<p><strong>Aim: </strong>Machine learning (ML) applications in pharmacovigilance remain limited and underexplored. Using data from the French National pharmacovigilance database (FNPV), this proof-of-concept study aimed to assess the feasibility of using a ML algorithm-eXtreme Gradient Boosting (XGBoost)-combined with SHapley Additive exPlanations (SHAP) analysis, to classify a well-defined drug-adverse reaction pair (warfarin-associated gastrointestinal bleeding) and identify risk factors for reporting this adverse reaction.</p><p><strong>Methods: </strong>We extracted individual case safety reports (ICSRs) involving warfarin from the FNPV. Following data preprocessing, the dataset was randomly split into a training set (75%) and an independent test set (25%). The XGBoost algorithm was trained to classify reports as either gastrointestinal bleeding or non-gastrointestinal bleeding adverse reactions. Model performance was assessed on the test set using multiple metrics: accuracy, recall, precision, F1-score and the area under the receiver operating characteristic curve (AUC-ROC). Feature importance and directional effects were interpreted using SHAP values.</p><p><strong>Results: </strong>A total of 2025 ICSRs involving warfarin were extracted from the FNPV. After preprocessing, 1045 ICSRs were retained. On the test set, the XGBoost model demonstrated an accuracy of 0.68, recall of 0.80, precision of 0.68, F1-score of 0.74 and an AUC-ROC of 0.716. SHAP analysis revealed the four most influential features in predicting gastrointestinal bleeding reporting: age, gastrointestinal bleeding risk, antiplatelet and history of renal dysfunction.</p><p><strong>Conclusion: </strong>We demonstrated the feasibility of using an XGBoost algorithm combined with SHAP analysis to pharmacovigilance data for the classification of adverse drug reactions and identify predictive features of reporting, following post hoc model interpretation by pharmacologists.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":"3503-3512"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13619036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148270332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Case-malformed signal detection and prioritisation using EUROmediCAT data for pharmacovigilance in pregnancy.","authors":"Hannah Johnson, Helen Dolk, Maria Loane, Christine Damase-Michel, Joanne Given, Hedvig Nordeng, Jorieke E H Bergman, Iain Carey, Elly Den Hond, Ester Garne, Florence Rouget, Lea Bruneau, Isabelle Monier, Anke Rissmann, Mary O'Mahony, Miriam Gatt, Renée Lutke, Joanna Sichitiu, Elisa Ballardini, Alessio Coi, Clara Cavero Carbonell, David Tucker, Joan Morris","doi":"10.1002/bcp.70645","DOIUrl":"10.1002/bcp.70645","url":null,"abstract":"<p><strong>Aim: </strong>Many women take medications during pregnancy. However, the risk to the fetus from most medications is uncertain. Congenital anomalies are one of the leading causes of infant death and contribute to long-term disability. Signal detection methods can be used to systematically identify possible medication-anomaly associations that require further investigation.</p><p><strong>Methods: </strong>Data on first trimester medication exposures in pregnancies with a congenital anomaly reported to 14 EUROmediCAT registries with a birth year of 2005-2018 were analysed. Case-malformed disproportionality analysis identified medication-anomaly signals using a disproportionality signal detection method. Identified signals were then compared to previous EUROmediCAT signal detection studies and ranked based on a proxy for the severity of impact at a population level using the number of estimated excess congenital anomaly cases within the exposed population and the average additional time in hospital over the first year of life. Generalized linear mixed models were used to assess confounding by birth year and registry within the top 20 ranked signals.</p><p><strong>Results: </strong>1611 medication-outcome pairs with at least three observations were analysed, and 153 signals for 63 different medications were identified. Of the top 20 ranked signals, 10 (involving nine medications) were prioritized for further independent investigation.</p><p><strong>Conclusion: </strong>The signals identified here are hypothesis forming only. Independent studies that adequately account for confounding are subsequently needed to evaluate if the identified signals are causal. Further investigation of signals with low population impact, but high potential individual risk is also recommended.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":"3586-3597"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13619031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148359642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}