British journal of clinical pharmacology最新文献

Population pharmacokinetics and optimized dosing of cefuroxime in critically ill patients. 危重患者头孢呋辛的人群药代动力学及优化剂量。

IF 3.1 3区医学

British journal of clinical pharmacology Pub Date : 2025-06-22 DOI: 10.1002/bcp.70144

Jaap W A Mouton, Julian D Machiels, Arthur M A Pistorius, Rob Ter Heine, Tim Frenzel, Nynke G L Jager, Jeroen A Schouten, Paddy K C Janssen, Rob E Aarnoutse, Roger J Brüggemann

{"title":"Population pharmacokinetics and optimized dosing of cefuroxime in critically ill patients.","authors":"Jaap W A Mouton, Julian D Machiels, Arthur M A Pistorius, Rob Ter Heine, Tim Frenzel, Nynke G L Jager, Jeroen A Schouten, Paddy K C Janssen, Rob E Aarnoutse, Roger J Brüggemann","doi":"10.1002/bcp.70144","DOIUrl":"https://doi.org/10.1002/bcp.70144","url":null,"abstract":"Cefuroxime is a second-generation cephalosporin widely used in the intensive care unit (ICU). ICU patients have high variability in interpatient pharmacokinetics (PK), but the extent of this variation is unclear. We performed an observational PK study in ICU patients. The objective of this study was to gain knowledge on the PK of cefuroxime and investigate target attainment of currently clinically applied dosing regimens. To identify the most suitable regimen the time above the minimal inhibitory concentration of the unbound drug (%fT > MIC) was calculated for different minimal inhibitory concentrations (MICs) and estimated Glomerular Filtration rates (eGFRs). Twenty patients were included with an average age of 66 years and modification of diet in renal disease (MDRD) (not indexed by BSA) of 90 [60-117.5] mL/min. A two-compartment model best fitted the data, with eGFR as a covariate. Probability of target attainment (PTA) was 43% for a 1500-mg q8h bolus dosage for the EUCAST break point of 8 mg/L for a typical individual with a eGFR of 60 mL/min. Dosing continuously using 4.5 g/day obtained 100% PTA for a typical individual with a eGFR up to 120 mL/min.","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144367918","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}

引用次数: 0

Letter to the editor of the Brit J Clin Pharmacol on Heuberger et al. 2025 https://doi.org/10.1002/bcp.70090. 致英国临床药理学杂志编辑的信，关于Heuberger等人。2025 https://doi.org/10.1002/bcp.70090。

IF 3.1 3区医学

British journal of clinical pharmacology Pub Date : 2025-06-20 DOI: 10.1002/bcp.70154

Markus Hinder, Vikram P Sinha

引用次数: 0

Switching disease-modifying therapies in patients with spinal muscular atrophy: A systematic review on effectiveness outcomes. 脊髓性肌萎缩症患者转换疾病改善疗法：疗效结局的系统评价

IF 3.1 3区医学

British journal of clinical pharmacology Pub Date : 2025-06-19 DOI: 10.1002/bcp.70145

Andrej Belančić, Elvira Meni Maria Gkrinia, Patrick Eustaquio, Andrea Katrin Faour, Dinko Vitezić

{"title":"Switching disease-modifying therapies in patients with spinal muscular atrophy: A systematic review on effectiveness outcomes.","authors":"Andrej Belančić, Elvira Meni Maria Gkrinia, Patrick Eustaquio, Andrea Katrin Faour, Dinko Vitezić","doi":"10.1002/bcp.70145","DOIUrl":"10.1002/bcp.70145","url":null,"abstract":"With multiple disease-modifying therapies now available, treatment switching has become an important clinical consideration in the management of spinal muscular atrophy (SMA). While some switches are prompted by suboptimal clinical response, more commonly they are driven by treatment burden, convenience, or adverse events. This systematic literature review aimed to synthesize existing evidence on therapy switching in SMA, focusing on clinical effectiveness and practical implications to support evidence-informed decision-making in a rapidly evolving therapeutic landscape. The review followed PRISMA guidelines and was registered with PROSPERO (CRD42024600221). A systematic search of PubMed/MEDLINE, Global Health and Embase was conducted between 11 and 14 October 2024. Eligible studies included clinical trials and real-world evidence (RWE) reports describing patients with genetically confirmed SMA who received nusinersen or risdiplam and subsequently switched to nusinersen, risdiplam or onasemnogene abeparvovec. Four studies met the inclusion criteria-three RWE studies and one clinical trial. The variability in measures of central tendency and variability among studies precluded the calculation of pooled summary values. Nonetheless, switching treatments was generally associated with stable motor function, with some improvements reported in selected outcome measures; ventilatory and nutritional support requirements remained largely unchanged. However, long-term outcomes and standardized data were limited. Future research should prioritize robust RWE and post-marketing surveillance to evaluate long-term safety and effectiveness, incorporate standardized switching protocols, and account for SMA genotype-phenotype variation.","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332460","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}

引用次数: 0

Spotlight commentary: Navigating the cutaneous side effects of chemotherapy. 焦点评论：化疗对皮肤的副作用。

IF 3.1 3区医学

British journal of clinical pharmacology Pub Date : 2025-06-17 DOI: 10.1002/bcp.70132

Sanja Brnić, Liborija Lugović-Mihić

引用次数: 0

Correction to "Minimizing prescribing errors: A phenomenological exploration of the views and experiences of independent prescribing pharmacists". 纠正“减少处方错误：独立处方药师观点与经验的现象学探索”。

IF 3.1 3区医学

British journal of clinical pharmacology Pub Date : 2025-06-16 DOI: 10.1002/bcp.70149

引用次数: 0

Metabolic fate of drugs of abuse and new psychoactive substances: A pilot study on a novel workflow using a zebrafish embryo model combined with human microdosing. 滥用药物和新型精神活性物质的代谢命运：使用斑马鱼胚胎模型结合人类微剂量的新工作流程的初步研究。

IF 3.1 3区医学

British journal of clinical pharmacology Pub Date : 2025-06-16 DOI: 10.1002/bcp.70140

Wellenberg K Simon, Tanja M Gampfer, Wagmann Lea, Schippers Philip, Herrmann Jennifer, Müller Rolf, Westphal Folker, Markus R Meyer

{"title":"Metabolic fate of drugs of abuse and new psychoactive substances: A pilot study on a novel workflow using a zebrafish embryo model combined with human microdosing.","authors":"Wellenberg K Simon, Tanja M Gampfer, Wagmann Lea, Schippers Philip, Herrmann Jennifer, Müller Rolf, Westphal Folker, Markus R Meyer","doi":"10.1002/bcp.70140","DOIUrl":"https://doi.org/10.1002/bcp.70140","url":null,"abstract":"Aim: The aim of this study was to develop a novel workflow to identify human urine biomarkers for drugs of abuse and new psychoactive substances. Metabolites of amphetamine, cocaine, LSD, MDMA, methamphetamine, THC, MDMB-CHMICA, and MDPPP were first identified in a zebrafish embryo (ZE) metabolism study followed by comparison to most abundant human metabolites in literature. Finally, metabolites were confirmed by human microdosing (HMD).Methods: ZEs 4 days post fertilization were exposed via immersion in Danieau's medium containing the compound or by injection into the caudal vein. After euthanization and freeze-drying, the ZEs were extracted using methanol. HMD was performed by oral administration of individual compound solutions according to HMD guidelines. Urine was collected spontaneously over 24 h and extracted via solid-phase extraction with and without conjugate cleavage. Samples were then analysed using reversed-phase liquid chromatography coupled to high resolution tandem mass spectrometry.Results: Overall, both ZE and HMD allowed identification of main human urine metabolites as described in literature. Exceptions for HMD were LSD due to the low applied dose and the cannabinoids, probably due to low oral bioavailability. Furthermore, ZE generally produced more metabolites compared to HMD, including conjugates.Conclusions: The proposed workflow of ZE exposure followed by HMD can provide quick and reliable data for prediction of analytical biomarkers for urinary drug screening. Following the initial identification of metabolites in ZE, human metabolites can afterwards be confirmed by HMD study. However, there are still challenges regarding HMD such as different routes of administration and detectability of applied low doses.","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309546","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}

引用次数: 0

Impact of diclofenac risk minimization measures addressing cardiovascular risk on analgesic use in musculoskeletal disorders. 针对心血管风险的双氯芬酸风险最小化措施对肌肉骨骼疾病中止痛药使用的影响

IF 3.1 3区医学

British journal of clinical pharmacology Pub Date : 2025-06-16 DOI: 10.1002/bcp.70142

Tomas Lasys, Yared Santa-Ana-Tellez, Satu J Siiskonen, Daniala L Weir, Rolf H H Groenwold, Helga Gardarsdottir

{"title":"Impact of diclofenac risk minimization measures addressing cardiovascular risk on analgesic use in musculoskeletal disorders.","authors":"Tomas Lasys, Yared Santa-Ana-Tellez, Satu J Siiskonen, Daniala L Weir, Rolf H H Groenwold, Helga Gardarsdottir","doi":"10.1002/bcp.70142","DOIUrl":"https://doi.org/10.1002/bcp.70142","url":null,"abstract":"Aims: In 2013, risk minimization measures (RMMs) were introduced in Europe to address the increased cardiovascular risk linked to diclofenac. This study aimed to assess the impact of those RMMs on analgesic use.Methods: Primary care data from CPRD GOLD (UK) were used. Patients newly diagnosed with musculoskeletal disorders during 2010-2019 were categorized into 4 cohorts, according to their diagnosis: acute (inflammatory) musculoskeletal conditions, chronic arthritic conditions, secondary arthritic conditions, or other painful conditions. The impact of the RMMs was studied using interrupted time series and survival analyses. Analyses were stratified by cardiovascular risk: (i) no risk factors or contraindications mentioned by RMMs; (ii) at least 1 risk factor; and (iii) at least 1 contraindication (prior cardiovascular events).Results: In total, 1 798 885 patients were included, with >28% having at least 1 cardiovascular risk factor and >7% having at least 1 contraindication for diclofenac. Initiation of diclofenac was already decreasing before the RMMs, but the RMMs were associated with a further immediate decrease in 2 cohorts (from -0.9 to -1.6%). No substantial difference in impact was observed depending on cardiovascular risk. The time from diagnosis to analgesic treatment increased after RMMs implementation, especially in patients with chronic arthritic conditions: median time increased from 4.2 to 7.6 months [95% confidence interval 4.0-4.5 and 7.4-7.8, respectively].Conclusion: The observed decrease of diclofenac initiation was unrelated to patients' cardiovascular risk. Continued prescribing of systemic diclofenac to patients with contraindications suggests limited impact of RMMs. Increased time from diagnosis to analgesic treatment suggests broader changes in analgesic prescribing practices.","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309545","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}

引用次数: 0

Unveiling predisposing factors for cefepime-induced neurotoxicity: A systematic review and meta-analysis. 揭示头孢吡肟诱导神经毒性的易感因素：一项系统回顾和荟萃分析。

IF 3.1 3区医学

British journal of clinical pharmacology Pub Date : 2025-06-16 DOI: 10.1002/bcp.70120

Harri Hardi, Melva Louisa, Indah Suci Widyahening, Julia Remi Chandra, Liganda Endo Mahata, Vivian Soetikno, Anggi Gayatri, Instiaty Instiaty

{"title":"Unveiling predisposing factors for cefepime-induced neurotoxicity: A systematic review and meta-analysis.","authors":"Harri Hardi, Melva Louisa, Indah Suci Widyahening, Julia Remi Chandra, Liganda Endo Mahata, Vivian Soetikno, Anggi Gayatri, Instiaty Instiaty","doi":"10.1002/bcp.70120","DOIUrl":"https://doi.org/10.1002/bcp.70120","url":null,"abstract":"Aims: The aim of this study was to elucidate the risk factors associated with the development of cefepime-induced neurotoxicity (CIN).Methods: This systematic review utilized keywords \"cefepime\" and \"neurotoxicity\", sourced from PubMed, Scopus, Web of Science and Google Scholar. Meta-analysis was conducted using a random effects model utilizing Mantel-Haenszel and inverse variance analysis for dichotomous and continuous outcomes, respectively.Results: Analysis of 23 articles revealed that estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 is the primary factor in CIN, with an odds ratio of 10.06 (95% confidence interval [CI] = 5.05-20.03, P < 0.0001). Other significant factors include central nervous system (CNS) abnormalities, age, body weight, albumin levels, diabetes mellitus, hypertension, chronic lung disease and inappropriate dosing. Subgroup analysis of continuous cefepime infusion utilization, based on several risk factors, indicated a lower odds ratio in comparison to intermittent infusion. For cefepime therapeutic drug monitoring (TDM) to determine potential CIN cases, the proposed trough concentration (Ctrough) threshold for intermittent infusion is 20 mg/L, while the steady-state concentration (Css) threshold for continuous infusion is 63 mg/L.Conclusions: Numerous risk factors are significantly associated with CIN, with renal impairment being the most significant. Continuous cefepime infusion is a potential strategy to mitigate CIN, in addition to dose adjustment and TDM.","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309547","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}

引用次数: 0

Pharmacokinetic-pharmacodynamic modelling in a clinical pilot study of rituximab in multiple sclerosis: Towards personalized dosing interval. 利妥昔单抗治疗多发性硬化症临床前期研究的药代动力学-药效学模型：面向个性化给药间隔。

IF 3.1 3区医学

British journal of clinical pharmacology Pub Date : 2025-06-14 DOI: 10.1002/bcp.70136

Trond Trætteberg Serkland, Silje Skrede, Erik Ingmar Hallin, Kjell-Morten Myhr, Øivind Torkildsen, Susanna Röblitz

{"title":"Pharmacokinetic-pharmacodynamic modelling in a clinical pilot study of rituximab in multiple sclerosis: Towards personalized dosing interval.","authors":"Trond Trætteberg Serkland, Silje Skrede, Erik Ingmar Hallin, Kjell-Morten Myhr, Øivind Torkildsen, Susanna Röblitz","doi":"10.1002/bcp.70136","DOIUrl":"https://doi.org/10.1002/bcp.70136","url":null,"abstract":"Aims: Rituximab (RTX) is used off-label for relapsing-remitting multiple sclerosis, although dosing regimens vary. Observational data suggest the standard 6-month interval may be extended and individualized. We aimed to develop a pharmacokinetic-pharmacodynamic (PKPD) model to describe patient-specific RTX concentrations and CD19+ lymphocyte counts.Methods: Thirteen treatment-naïve patients initiated RTX treatment with 1000 mg intravenously. Blood samples were collected at 6 time points during the following 6 months. RTX concentrations and CD19+ lymphocyte counts were used to compare different PKPD using the nonlinear mixed-effects software Monolix.Results: Initial pharmacokinetics of RTX could be described by a 1-compartment model with nonlinear target-mediated elimination of rituximab. Introduction of CD19+ lymphocyte counts as a pharmacodynamic marker resulted in comparable performance of a 1-compartment and a 2-compartment model and can provide descriptions of RTX concentrations and CD19+ lymphocyte counts in individual patients. In both models, nonspecific clearance (CL) contributes approximately 10 times more to the overall elimination than target-mediated clearance (kdeg,1; CL [1/day] = 0.075 ± 0.035 [median 0.061], kdeg,1 [mm-3/day] = 0.125 ± 0.311 [median 0.007] and CL [1/day] = 0.036 ± 0.027 [median 0.026], kdeg,1 [mm-3/day] = 0.004 ± 0.002 [median 0.003]).Conclusions: The PKPD models were able to describe the data both in patients exhibiting enduring CD19+ lymphocyte depletion and in patients exhibiting signs of early CD19+ lymphocyte repopulation. Additional data are required to validate and advance models for prediction of repopulation dynamics and, eventually, individualized RTX dosing.","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293306","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}

引用次数: 0

From cramming to binge-watching: Integrating documentary-based assessment into a pharmacology and toxicology curriculum-a qualitative study. 从死记硬背到疯狂观看：将基于纪录片的评估整合到药理学和毒理学课程中——一项定性研究。

IF 3.1 3区医学

British journal of clinical pharmacology Pub Date : 2025-06-13 DOI: 10.1002/bcp.70134

Narin Akrawi, Heleen van der Sijs, Floor van Rosse

{"title":"From cramming to binge-watching: Integrating documentary-based assessment into a pharmacology and toxicology curriculum-a qualitative study.","authors":"Narin Akrawi, Heleen van der Sijs, Floor van Rosse","doi":"10.1002/bcp.70134","DOIUrl":"https://doi.org/10.1002/bcp.70134","url":null,"abstract":"Aims: In the context of pharmacology and toxicology education, there is a growing shift toward programmatic assessment models that prioritize longitudinal learning, reflection and development of higher-order cognitive skills. As part of this transition, we are exploring alternative and more meaningful forms of assessment. This qualitative study investigates students' perceptions of an innovative assessment format-documentary-based assessment-introduced in the interdisciplinary Minor ToXiC course, which covers the life cycle of a medicine and includes topics such as pharmacology and toxicology.Methods: As part of the assessment programme within Minor ToXiC, students watched selected documentaries and completed an assessment consisting of 6 open-ended questions. Questions 1- 5 prompted students to reflect on the documentary content and link it to the course material of the minor, while question 6 invited them to evaluate how they experienced this form of assessment. Responses to question 6 were analysed thematically.Results: Three main categories emerged from the themes. First, students highlighted the educational value of documentaries, describing how visual and narrative elements helped them better retain information, connect theory to practice, and reflect critically on ethical, social and pharmacological dimensions of real-world cases. Second, the format was perceived as motivating due to the autonomy it allowed. Third, students identified key structural conditions necessary for the effectiveness of this format.Conclusion: Overall, documentary-based assessment appears to be a promising addition in a programmatic assessment-based curriculum. To optimize its impact, careful attention must be paid to the design, timing and integration of this assessment method within the curriculum.","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293305","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}

引用次数: 0