British journal of clinical pharmacology最新文献

{"title":"Real-world population pharmacokinetics of tezacaftor-ivacaftor in children with cystic fibrosis: The SYM-CF study.","authors":"Steffie E M Vonk, Suzanne W J Terheggen-Lagro, Eric G Haarman, Hettie M Janssens, Anke-Hilse Maitland-van der Zee, E Marleen Kemper, Ron A A Mathôt","doi":"10.1002/bcp.70131","DOIUrl":"https://doi.org/10.1002/bcp.70131","url":null,"abstract":"<p><strong>Aims: </strong>The clinical effectiveness of tezacaftor-ivacaftor in children with cystic fibrosis (cwCF) varies; some patients respond while others do not or have adverse effects. The pharmacokinetics (PK) of tezacaftor-ivacaftor are inadequately published, especially in children. Knowledge of the PK in this cohort in relation to clinical outcomes may give further insight into the drug's exposure-response relationship and its associated interindividual variability. The aim of this study was to assess the real-world PK of tezacaftor-ivacaftor in cwCF.</p><p><strong>Methods: </strong>A prospective, observational PK study was performed in cwCF using tezacaftor-ivacaftor. PK samples were obtained by dried blood spots at home and during routine outpatient hospital visits. Population PK (popPK) models were created using nonlinear mixed-effects modelling. Due to data scarcity, prior information from adolescent/adult PK models was required.</p><p><strong>Results: </strong>The study involved 21 children (age 6-17 years, weight 24-70 kg). Novel popPK models were created for tezacaftor-ivacaftor and its main metabolites. Variability in PK was explained by variation in body weight. The area under the curve of tezacaftor-ivacaftor varied significantly within and across age groups, which corresponded to the reported area under the curve in the product information. Maximum concentration and elimination half-lives closely matched adult reported values.</p><p><strong>Conclusions: </strong>This is the first study to investigate the popPK of tezacaftor-ivacaftor in cwCF. The established models can be used for more personalized dosing in children experiencing suboptimal efficacy, adverse effects, drug-drug interactions, or where adherence is a concern.</p>","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":"144282418","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":"Neurotoxicity from inordinate valacyclovir dosage in an elderly woman with stage 5 chronic kidney disease.","authors":"Juan A Vasquez Vasquez, Kyle D Pires, Belbina J Pereira, Kimberly M Brown, James A Langston, Charles E Langs, Robert S Hoffman","doi":"10.1002/bcp.70138","DOIUrl":"https://doi.org/10.1002/bcp.70138","url":null,"abstract":"<p><p>Unadjusted doses of valacyclovir can cause neurotoxicity in patients with chronic kidney disease. There are no well documented reports of valacyclovir or acyclovir toxicity providing pre- and postdialysis concentrations of acyclovir in the blood, dialysate and urine of acutely neurotoxic patients. We report an elderly woman with stage 5 chronic kidney disease who developed neurotoxicity after being prescribed unadjusted doses of valacyclovir and provide measurements of the amount of the drug eliminated through haemodialysis vs. native renal clearance. The patient's estimated body-burden of drug before the first session of dialysis was estimated at 580.3 mg. During the first haemodialysis session acyclovir plasma concentrations decreased from 8.8 to 3.2 mg/L (63.6%). Her body-burden of drug before the second session of haemodialysis was estimated as 131.9 mg. During the 2.5 h of the second dialysis session a total of 66.6 mg was eliminated based on measured dialysate concentrations. Urinary elimination was 17.7 mg over 30 h. Despite minimal urinary elimination her blood concentration fell from 8.8 to 0.88 mg/L with a total of 4.5 h of haemodialysis. Haemodialysis appears to be an effective method of eliminating acyclovir, especially in patients with advanced kidney disease.</p>","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":"144282416","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":"Prescription drug use in breastfeeding mothers and infant exposure: A register-based cohort study.","authors":"Ditte Resendal Gotfredsen, Ida M Heerfordt, Christoffer Storm Baden, Henrik Horwitz, Christina Gade, Jon Trærup Andersen","doi":"10.1002/bcp.70139","DOIUrl":"https://doi.org/10.1002/bcp.70139","url":null,"abstract":"<p><strong>Aims: </strong>Breast milk is the optimal infant nutrition; however, many infants may be exposed to prescription drugs if used by their mothers during breastfeeding. The aim of this study was to evaluate the prevalence and patterns of prescription drug use among breastfeeding mothers and to assess the availability of relative infant dose information for these drugs.</p><p><strong>Methods: </strong>This population-based cohort study was conducted using nationwide Danish register data from January 2006 to December 2022. All registered mother-infant pairs were included during periods of exclusive breastfeeding. The national health registers were used to identify live births, breastfeeding status and prescription drug use by mothers during exclusive breastfeeding.</p><p><strong>Results: </strong>Among 534 080 exclusively breastfed infants, 290 845 (54.5%) were breastfed by mothers who used at least 1 prescription drug during the breastfeeding period. The drugs were primarily for haemorrhoids, contraception, infections and pain management. Among individual systemic drugs used during exclusive breastfeeding, 51.5% lacked information on relative infant dose.</p><p><strong>Conclusions: </strong>This large-scale cohort study reveals a high prevalence of prescription drug use during exclusive breastfeeding, often involving drugs with unknown safety profiles regarding their transfer into human milk. These findings highlight the need for updated regulatory measures and increased efforts by pharmaceutical companies to ensure reliable infant safety data.</p>","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":"144282417","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 clinical toxicity of advanced therapy medicinal products.","authors":"Fraser J H Henderson, Simon L Hill","doi":"10.1002/bcp.70104","DOIUrl":"https://doi.org/10.1002/bcp.70104","url":null,"abstract":"<p><strong>Aims: </strong>Advanced Therapy Medicinal Products (ATMPs) use genes, tissues or cells to offer transformative treatments for a range of diseases. They are associated with different safety challenges when compared to established therapeutics, such as small chemical entities or monoclonal antibodies, due to immunogenicity, off-target effects and organ-specific toxicities. This review evaluates the current clinical evidence on ATMP toxicity, highlighting key mechanisms of toxicity and describing approaches to risk management.</p><p><strong>Methods: </strong>A scoping review was conducted using the MEDLINE and Embase databases to identify studies reporting toxicities associated with gene therapy medicinal products (GTMPs), somatic-cell therapy medicinal products, tissue-engineered products and combined ATMPs. Data were extracted and collated qualitatively, focusing on acute and chronic clinical toxicity.</p><p><strong>Results: </strong>Acute toxicity, such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome were most often reported in GTMPs, particularly chimeric antigen receptor T-cell therapies. Chronic risks of GTMPs include genotoxicity and tumorigenicity, especially with high-dose adeno-associated virus-based therapies. Somatic-cell therapy medicinal products carry risks of immunological toxicity and tumour formation, particularly in stem cell-based approaches. Tissue-engineered products present challenges of biocompatibility, scaffold degradation and host integration. Management strategies to mitigate anticipated toxicity include preconditioning regimens, safer vector design, immunosuppressive therapies (e.g. tocilizumab) and long-term monitoring.</p><p><strong>Conclusion: </strong>ATMPs offer significant therapeutic promise but require robust safety assessments and proactive risk management plans to address their complex potential toxicity profiles. Personalized approaches, advanced preclinical models and stringent regulatory oversight are essential to ensure these therapies fulfil their potential without compromising patient safety.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282419","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":"Nonchemotherapy drug-induced cytopenias: A cost-of-illness study using the microcosting methodology based on real-world data.","authors":"Ivana Stević, Slobodan M Janković, Nemanja Petrović, Nataša Čanak-Baltić, Valentina Marinković, Dragana Lakić","doi":"10.1002/bcp.70122","DOIUrl":"https://doi.org/10.1002/bcp.70122","url":null,"abstract":"<p><strong>Aims: </strong>Our study aimed to determine the healthcare utilization and costs of nonchemotherapy drug-induced cytopenias and analyse the main drivers of costs.</p><p><strong>Methods: </strong>This cost-of-illness study was conducted using the microcosting (bottom-up) approach based on real-world data. Data on the patients who developed leucopenia, anaemia or thrombocytopenia as nonchemotherapy drug-induced blood disorders were extracted from records of the inpatients treated in a tertiary care university hospital.</p><p><strong>Results: </strong>The study included 46, 71 and 80 cases of leucopenia, anaemia and thrombocytopenia, respectively. Leucopenia had the highest costs per case (average: 200 928.4, median: 176 078.4 Serbian dinars [RSD], interquartile range: 171 223.4 RSD), followed by thrombocytopenia (average: 115 065.2, median: 89 732.4 RSD, interquartile range: 77 755.9 RSD) and anaemia (average: 109 502.5, median: 90 267.3 RSD, interquartile range: 74 225.1 RSD). These costs expressed as Gross Domestic Product per capita based on purchasing power parity were 6.97, 2.85 and 2.84% for leucopenia, anaemia and thrombocytopenia, respectively. In leucopenia, 48.9% of the costs were the costs of drugs, while in anaemia and thrombocytopenia, the majority of the costs were due to the length of hospitalization (38.6 and 34.7%, respectively). The factors with the greatest influence on the total costs of anaemia and thrombocytopenia were the length of hospitalization and the number of computed tomography scans, while the cost of leucopenia treatment was most influenced by survival status, age and the number of laboratory tests.</p><p><strong>Conclusions: </strong>Our study showed that the use of healthcare services and costs caused by nonchemotherapy drugs are considerable. Proactive strategies to manage and prevent drug-induced cytopenias should be considered.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144265295","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 long-term statin therapy on age-related macular degeneration: A nationwide population-based study.","authors":"Po-Yu Jay Chen, Jyun-Lin Lee, Lei Wan, Hui-Ju Lin, Wen-Lu Chen, San-Ni Chen, Chun-Ju Lin, Jane-Ming Lin, Chun-Ting Lai, Ning-Yi Hsia, Yu-Te Huang, Yi-Yu Tsai, Heng-Jun Lin, Yow-Wen Hsieh, Yih-Dih Cheng, Fuu-Jen Tsai, Chien-Chih Chou, Peng-Tai Tien","doi":"10.1002/bcp.70128","DOIUrl":"https://doi.org/10.1002/bcp.70128","url":null,"abstract":"<p><strong>Aims: </strong>Age-related macular degeneration (AMD) is a leading cause of vision loss worldwide among older adults. Although some studies propose that statins could reduce AMD risk and progression, others report conflicting findings. This study aimed to evaluate the impact of statin use on the incidence of AMD.</p><p><strong>Methods: </strong>This study used Taiwan's National Health Insurance Research Database (2000-2021) with the LGTD2000 cohort. Participants were categorized into statin users (≥6 months, 2001-2020) and nonusers. AMD incidence was analysed using Cox regression and Kaplan-Meier methods, with propensity score matching applied to report adjusted hazard ratios (AHRs) and confidence intervals (CIs).</p><p><strong>Results: </strong>After adjusting for confounding factors, statin use for over 2 years was associated with a significantly lower risk of AMD compared to nonstatin users (AHR = 0.79, 95% CI: 0.69-0.91). Subgroup analyses demonstrated that long-term statin use (≥730 days) showed protective associations across most sex and age groups. Specifically, risk reduction was observed for both non-neovascular AMD (AHR = 0.84, 95% CI: 0.70-1.02) and neovascular AMD (AHR = 0.72, 95% CI: 0.59-0.88). Furthermore, dose-response analysis revealed that higher cumulative statin exposure was associated with a decreased AMD risk, while lower cumulative exposure was associated with an increased risk.</p><p><strong>Conclusion: </strong>This study indicated that prolonged statin use exceeding 2 years was associated with a significantly decreased risk of developing both non-neovascular and neovascular AMD.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144265293","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":"Prescribing competence: The pros and cons of different methods for assessment.","authors":"David J Brinkman, Erik M Donker, Jelle Tichelaar","doi":"10.1002/bcp.70125","DOIUrl":"https://doi.org/10.1002/bcp.70125","url":null,"abstract":"<p><p>Evaluating a medical graduate's competence in rational prescribing is challenging. With the aim to guide and inspire teachers, this narrative review explores different methods that can be used to assess prescribing competence. Each method has its own advantages and disadvantages, and thus a mix of different assessment methods is needed throughout the undergraduate curriculum to ensure that medical students are competent prescribers. Miller's pyramid of clinical competence might help identify the most suitable assessment at each stage of the curriculum. Programmatic assessment, whereby progress is assessed at different times throughout the curriculum, is promising and offers potential long-term advantages, especially in fostering continuous learning.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144265298","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":"Longitudinal non-cancer pain management patterns and risk of adverse outcomes in older adults: Insights from group-based multi-trajectory modelling.","authors":"I-Tzu Chen, Shih-Tsung Huang, Chih-Kuang Liang, Ming-Yueh Chou, Ching-Hui Loh, Liang-Kung Chen, Fei-Yuan Hsiao","doi":"10.1002/bcp.70117","DOIUrl":"https://doi.org/10.1002/bcp.70117","url":null,"abstract":"<p><strong>Aims: </strong>The long-term impact of different non-cancer pain management strategies in older adults remains poorly understood. This population-based retrospective cohort study aimed to identify distinct trajectories of chronic non-cancer pain management and examine their associations with adverse clinical outcomes in older adults, stratified by frailty status.</p><p><strong>Methods: </strong>Using Taiwan's National Health Insurance database, we included older adults (≥65 years) who initiated non-steroidal anti-inflammatory drugs (NSAIDs) in 2010 and followed them for 8 years. Participants were stratified by frailty status using the multimorbidity frailty index. Group-based multi-trajectory modelling and Cox proportional hazards models were employed to identify distinct trajectories of chronic non-cancer pain management (including medications [i.e., NSAIDs, paracetamol, muscle relaxants and psychotropic agents] and non-pharmacological physical therapy) and to assess the associations between trajectory groups and subsequent clinical outcomes.</p><p><strong>Results: </strong>Among 24 539 participants (mean age 72.7, 58.9% female), four distinct trajectories were identified: short-term (27.6%), mild (31.9%), moderate (21.7%) and extensive (18.9%) utilization. Compared to the short-term group, the extensive utilization group were significantly associated with higher risks of unplanned hospitalization (adjusted hazard ratio [aHR]: 1.36, 95% confidence interval [CI] 1.24-1.48), all-cause hospitalization (aHR: 1.43, 95% CI 1.35-1.52) and incident dementia (aHR: 1.27, 95% CI 1.04-1.54). For dialysis, only the extensive group was associated with higher risk in the age-sex adjusted model (HR: 2.06, 95% CI: 1.00-4.22), but significance was attenuated after frailty adjustment. No significant differences in all-cause mortality were observed after full adjustment.</p><p><strong>Conclusions: </strong>These findings highlight that extensive long-term utilization of pain management strategies in older adults is associated with increased risks of adverse outcomes, particularly hospitalizations and incident dementia, especially among fit older adults, emphasizing the need for careful monitoring and personalized approaches to pain management in older populations, balancing effective pain control with minimization of potential long-term risks.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144265294","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":"Patient-reported satisfaction and adherence with DOACs: Real-life data from the DASS experience.","authors":"Antonella Mameli, Francesco Marongiu, Doris Barcellona","doi":"10.1002/bcp.70129","DOIUrl":"https://doi.org/10.1002/bcp.70129","url":null,"abstract":"","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144265297","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":"Contribution of Addictovigilance data to assess adverse-events linked to psychoactive substances in children and adolescents.","authors":"Hélène Peyrière, Anne Batisse, Nathalie Fouilhé Sam-Laï, Amélie Daveluy, Christine Fournier-Choma, Sylvie Deheul, Cécile Chevalier, Clémence Lacroix, Valérie Gibaja, Aurélie Aquizerate, Stéphanie Pain, Emilie Jouanjus, Marie-Christine Picot, Erika Nogue","doi":"10.1002/bcp.70133","DOIUrl":"https://doi.org/10.1002/bcp.70133","url":null,"abstract":"<p><strong>Aims: </strong>We sought to characterize adverse events and deaths associated with the use of psychoactive substances in children and adolescents.</p><p><strong>Methods: </strong>Two French Addictovigilance databases were analysed: spontaneous reports and deaths over the period 2016-2021, in subjects aged 10-<18 years. An unsupervised classification was implemented on consumption data (medications or nondrug substances [NDS]) to identify subject clusters.</p><p><strong>Results: </strong>A total of 1544 spontaneous reports were analysed, comprising mainly boys (65.6%), aged on average 16 ± 1 years. Four clusters were identified: The cannabinoids users cluster (n = 597) was typified by the use of cannabis or/and synthetic cannabinoids (95.1%), with psychiatric (67.7%) and digestive disorders (16.7%). The medications/solvents/cannabidiol users cluster (n = 699) was distinguished by the use of medications or NDS including nitrous oxide/cannabidiol, with mainly neurological disorders (46.5%). The polydrug users cluster (n = 177) includes polyusers (98.3%) of NDS and medications. These users mainly have substance use disorders (63.8%). The psychotropic medications users cluster (n = 71) was characterized by the use of psychotropic medications. This cluster appeared to be correlated with psychiatric and organic disorders. The death database recorded 44 deaths, mainly in boys (61.4%) aged over 15 years. The main substances involved in the deaths were NDS (70.5%) and methadone. In 68.2% of cases, a single substance was responsible for the death.</p><p><strong>Conclusion: </strong>The adverse events related to the abuse of psychoactive substances identified in children and adolescents and the emerging signals show the need for increased surveillance and the implementation of prevention campaigns adapted to each group of consumers.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144265281","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}