British journal of clinical pharmacology最新文献

{"title":"Probability of pharmacokinetic/pharmacodynamic target attainment for different piperacillin/tazobactam dosing regimens in renally impaired patients in a non-intensive care unit setting.","authors":"Emma Dohmann, Stefan Hagel, Max Kurlbaum, Paul Schellong, Oliver Scherf-Clavel, Güzin Surat","doi":"10.1002/bcp.70153","DOIUrl":"https://doi.org/10.1002/bcp.70153","url":null,"abstract":"<p><strong>Aims: </strong>To optimize antibiotic therapy for pathogens classified as susceptible, increased exposure (I), an increased exposure of piperacillin/tazobactam (PTZ) is required. However, dosing recommendations are currently only available for patients with normal renal function. The aim of the study was to assess whether the recommended dosages of PTZ for patients with impaired renal function achieve adequate pharmacokinetic/pharmacodynamic (PK/PD) targets for pathogens classified as susceptible, increased exposure (I).</p><p><strong>Methods: </strong>Overall, 49 patients with impaired renal function were included in this study (estimated glomerular filtration rate [eGFR] 20-40 mL/min: n = 20; eGFR <20 mL/min: n = 19; intermittent haemodialysis: n = 10). Peak, trough and between-dosing interval piperacillin concentrations were determined. The primary endpoint of the study was the probability of target attainment (PTA) for a conservative (fT 60% > minimal inhibitory concentration) and an aggressive PK/PD target (fT 100% > 4× minimal inhibitory concentration). First, a population pharmacokinetic model was developed followed by a model-based simulation.</p><p><strong>Results: </strong>For the conservative PK/PD target, a PTA of >90% is achieved in all patients receiving intermittent short infusions, following the dosing recommendations outlined in the Summary of Product Characteristics (SmPC). For the more aggressive target, the PTA was <15% across all groups when using short infusions with SmPC dosing. Only continuous infusion with an increased daily dose in patients with eGFRs of 30 and 40 mL/min achieved a PTA of >90% in all patients.</p><p><strong>Conclusions: </strong>Dosing according to the SmPC is only sufficient to achieve a conservative PK/PD target. In comparison, simulating an increased dosing with continuous administration attained an aggressive PK/PD target. Offering alternative dosing regimens may be of interest for severe infections with difficult to treat foci caused by Pseudomonas aeruginosa even in non-intensive care unit patients.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526479","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 integration of the British Pharmacological Society's prescription safety assessment into the WHO 6-step model of rational pharmacotherapy in a Turkish medical school.","authors":"Sinem Ezgi Gülmez, Gülnihal Özcan, Hakan S Orer","doi":"10.1002/bcp.70146","DOIUrl":"https://doi.org/10.1002/bcp.70146","url":null,"abstract":"<p><strong>Aims: </strong>At Koç University School of Medicine, a one-week rational pharmacotherapy (RPHM) programme, modelled after WHO 6-step, has been introduced in the fourth-year curriculum to improve prescription skills. For efficient problem-based learning (PBL) sessions on a prespecified topic, students need to brush up on basic pharmacology knowledge, so we implemented the British Pharmacological Society (BPS)-Prescribing Safety Assessment (PSA) related to prescription skills in eight competencies. A survey-based study was initiated to evaluate students' self-confidence.</p><p><strong>Methods: </strong>The study included 101 medical students in two groups (respiratory tract infections, urinary infections/sexually transmitted diseases) in 2020-2023. Students were required to take BPS-PSA, prepare personal formularies and prove their ability to manage simulated patients in objective structured clinical examinations (OSCE) settings. A 15-item PSA-invigilated paper with an eight-item practice paper was explicitly prepared by BPS to match indications, tailored according to local formularies and regulations. Self-efficacy surveys were filled out before, during and after completion of the programme. Survey results were analysed concurrently with OSCE and BPS-PSA performances.</p><p><strong>Results: </strong>The number of students and gender distributions were similar in all groups. Average final grades ranged from 74-82 points for OSCE, and 43-59 for BPS-PSA. All groups did well in OSCE (92.1% aggregate pass rate). Survey results showed significant increase in self-efficacy levels measured at different task categories as the training progressed. The highest scores in PSA were for dose calculation (88.3%) and lowest for communication (33.01%).</p><p><strong>Conclusions: </strong>Implementing the PSA to WHO 6-step model provided complete assessment of learning environment and student progress. The new teaching programme supports students in developing their prescribing skills, allowing benchmarking in an international setting.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144483086","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 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":"<p><p>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.</p>","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}

{"title":"Letter to the editor of the Brit J Clin Pharmacol on Heuberger et al. 2025 https://doi.org/10.1002/bcp.70090.","authors":"Markus Hinder, Vikram P Sinha","doi":"10.1002/bcp.70154","DOIUrl":"10.1002/bcp.70154","url":null,"abstract":"","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332459","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":"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":"<p><p>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.</p>","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}

{"title":"Spotlight commentary: Navigating the cutaneous side effects of chemotherapy.","authors":"Sanja Brnić, Liborija Lugović-Mihić","doi":"10.1002/bcp.70132","DOIUrl":"https://doi.org/10.1002/bcp.70132","url":null,"abstract":"","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315944","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":"Correction to \"Minimizing prescribing errors: A phenomenological exploration of the views and experiences of independent prescribing pharmacists\".","authors":"","doi":"10.1002/bcp.70149","DOIUrl":"https://doi.org/10.1002/bcp.70149","url":null,"abstract":"","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":"144309544","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":"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":"<p><strong>Aim: </strong>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).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","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}

{"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":"<p><strong>Aims: </strong>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.</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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].</p><p><strong>Conclusion: </strong>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.</p>","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}

{"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":"<p><strong>Aims: </strong>The aim of this study was to elucidate the risk factors associated with the development of cefepime-induced neurotoxicity (CIN).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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 (C_trough) threshold for intermittent infusion is 20 mg/L, while the steady-state concentration (C_ss) threshold for continuous infusion is 63 mg/L.</p><p><strong>Conclusions: </strong>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.</p>","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}