Basic & Clinical Pharmacology & Toxicology最新文献

{"title":"Doctor–Patient Deprescribing Conversations: A Multidisciplinary Analysis of Quality Assurance Recordings","authors":"Kelly E. Tenzek,&nbsp;Huei-Yen Winnie Chen,&nbsp;Laura A. Brady,&nbsp;Connor Wurst,&nbsp;Matt Cosmai,&nbsp;Jennifer Carlson,&nbsp;Andrew Baumgartner,&nbsp;Ranjit Singh,&nbsp;Robert G. Wahler Jr.,&nbsp;Scott Monte","doi":"10.1111/bcpt.70122","DOIUrl":"https://doi.org/10.1111/bcpt.70122","url":null,"abstract":"<div>\u0000 \u0000 <p>Previous work in deprescribing interactions primarily involved surveys, interviews or reviews; there is a gap in utilizing real-time doctor–patient communication to understand what strategies physicians use to deprescribe and how patients respond. To move research methodology in this direction, our multidisciplinary team brought together professionals from biomedical, cognitive and social sciences to collaborate with a primary care practice and analyse nine quality-assurance recordings of doctor–patient visits. Eligible patients were 60 years or older and prescribed two or more medications. Through collaborative mixed-method analysis, we identified outcomes and themes of deprescribing conversations. An additional layer of analysis was conducted based on qualitative interviews with two deprescribing physicians for a conversation about physicians' decision-making process in initiating and responding to patient concerns in the interaction. Interplay between patient, physician and system factors was noted, highlighting the key role of health care team collaboration to support deprescribing. Our innovative research design enables a better understanding of deprescribing processes in a primary care setting and has implications for future research including patients, caregivers and community providers.</p>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 5","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145146976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hexafluoropropylene Oxide Trimer Carboxylic Acid in Biological Systems","authors":"Bei Yang,&nbsp;Jie Liu","doi":"10.1111/bcpt.70117","DOIUrl":"https://doi.org/10.1111/bcpt.70117","url":null,"abstract":"<p>As a replacement for phased-out perfluorooctanoic acid (PFOA), hexafluoropropylene oxide trimer carboxylic acid (HFPO-TA) exhibits environmental persistence and multisystem toxicity, affecting reproductive, hepatic, neurological and endocrine functions. Despite its industrial adoption, emerging studies reveal bioaccumulation risks and mechanistic toxicity through oxidative stress, metabolic disruption and inflammation. This review synthesizes evidence of HFPO-TA's health impacts, highlighting unresolved female reproductive toxicity and dose–response relationships.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 5","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70117","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145146951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multidimensional Evaluation of Lisdexamfetamine: Pharmacology, Therapeutic Use, Toxicity and Forensic Implications","authors":"Mariana Silva-Carvalho,&nbsp;Daniel José Barbosa,&nbsp;Diana Dias da Silva,&nbsp;Ricardo Jorge Dinis-Oliveira","doi":"10.1111/bcpt.70111","DOIUrl":"https://doi.org/10.1111/bcpt.70111","url":null,"abstract":"<p>Lisdexamfetamine (LDX), a prodrug of <i>d</i>-amphetamine, is widely used in the pharmacological treatment of neuropsychiatric disorders such as attention-deficit/hyperactivity disorder (ADHD) and binge eating disorder (BED). Chemically, it consists of the amino acid lysine linked to <i>d</i>-amphetamine. Its enzymatic conversion to <i>d</i>-amphetamine sets the stage for a prolonged and controlled release, influencing its clinical profile and differentiating it from other stimulant medications. As a central nervous system stimulant, LDX primarily acts by increasing the release of neurotransmitters, particularly dopamine and noradrenaline, in the brain. Clinically, this enhanced availability of neurotransmitters is believed to contribute to improvements in attention, focus and impulse control in individuals with ADHD. The side effects of LDX include insomnia, decreased appetite, weight loss and xerostomia. This work reviews the pharmacological mechanisms, clinical applications and forensic considerations associated with its use. It is expected that clinicians, researchers and policymakers have a comprehensive understanding of the pharmacological and toxicological aspects of LDX.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 5","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70111","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145135710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolomics and Network Pharmacology Revealed the Mechanism of Feining Mixture Against Respiratory Syncytial Virus Pneumonia","authors":"Chengdou Xie,&nbsp;Qianyu Liu,&nbsp;Ping Lan,&nbsp;Linxiu Peng,&nbsp;Siqing Chen","doi":"10.1111/bcpt.70114","DOIUrl":"10.1111/bcpt.70114","url":null,"abstract":"<div>\u0000 \u0000 <p>Respiratory syncytial virus (RSV) is a leading etiological agent of pneumonia, particularly affecting infants under 2 years and elderly populations, with characteristic clinical manifestations including fever, cough and wheezing. Although Feining mixture—a traditional Chinese medicine formulation based on the classical Maxing Shigan Decoction from the ‘Treatise on Febrile Diseases’—has shown clinical efficacy in ameliorating symptoms of viral pneumonias including RSV infection, its precise pharmacological mechanisms remain undefined. Through serum metabolomics and network pharmacology approaches, we systematically identified RSV-associated metabolic disturbances and characterised Feining mixture's regulatory effects on these pathological alterations. Our investigations revealed that Feining mixture significantly attenuated pulmonary inflammation, as evidenced by reduced pro-inflammatory cytokine levels in bronchoalveolar lavage fluid and improved histopathological features in RSV-infected mice. Metabolomic profiling identified 49 differentially expressed metabolites and 14 perturbed metabolic pathways. Network pharmacology and molecular docking analyses predicted the involvement of TP53, AKT1 and STAT3 as core targets, suggesting modulation of PI3K/AKT and TNF signalling pathways. These predictions were experimentally validated through qPCR and Wb analyses, which confirmed that Feining mixture's therapeutic effects are mediated through selective inhibition of the PI3K/AKT1 signalling cascade. These findings provide novel mechanistic insights into Feining mixture's anti-RSV activity, establishing its therapeutic potential through multi-target modulation of critical inflammatory and metabolic pathways.</p>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “Capillary Sampling Enables Venetoclax Concentration Measurement in Acute Myeloid Leukaemia Within Academic Multicentre Trial”","authors":"","doi":"10.1111/bcpt.70120","DOIUrl":"10.1111/bcpt.70120","url":null,"abstract":"<p>\u0000 <span>Kytölä, S.</span>, <span>Kurkela, M.</span>, <span>Kiiski, J.</span>, <span>Vänttinen, I.</span>, <span>Ruokoranta, T.</span>, <span>Partanen, A.</span>, <span>Holopainen, A.</span>, <span>Pyörälä, M.</span>, <span>Kuusisto, M.</span>, <span>Siitonen, T.</span>, <span>Koskela, S.</span>, <span>Rimpiläinen, J.</span>, <span>Ettala, P.</span>, <span>Kuusanmäki, H.</span>, <span>Niemi, M.</span>, <span>Backman, J.</span> and <span>Kontro, M.</span> (<span>2025</span>), <span>Capillary Sampling Enables Venetoclax Concentration Measurement in Acute Myeloid Leukaemia Within Academic Multicentre Trial</span>. <i>Basic Clin Pharmacol Toxicol</i>, <span>136</span>: e70041, https://doi.org/10.1111/bcpt.70041.\u0000 </p><p>In this article, we have added the funding information in the Acknowledgement section as follows:</p><p>Open access publishing was facilitated by University of Helsinki, as part of the Wiley–FinELib agreement.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70120","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hesperidin Mitigates Bleomycin-Induced Testicular and Spermatological Damage in Rats","authors":"İdris Ayhan,&nbsp;Nese Basak Turkmen,&nbsp;Saadet Alan,&nbsp;Muhterem Aydin,&nbsp;Osman Ciftci","doi":"10.1111/bcpt.70119","DOIUrl":"10.1111/bcpt.70119","url":null,"abstract":"<div>\u0000 \u0000 <p>Bleomycin (BLM), a chemotherapeutic agent commonly used in cancer treatment, is associated with oxidative stress and testicular toxicity, leading to impaired reproductive health. Hesperidin (HES), a citrus-derived flavonoid with strong antioxidant properties, has the potential to counteract these adverse effects. This study aimed to evaluate the protective effects of HES against the reproductive toxicity induced by BLM, focusing on oxidative stress, sperm characteristics and histological changes in the male reproductive system. Thirty-two rats were divided into four groups: Control, BLM, HES and BLM + HES. BLM was administered intraperitoneally at 10 mg/kg twice a week, while HES was given orally at 50 mg/kg/day for 30 days. The findings revealed that BLM induced significant oxidative stress by promoting lipid peroxidation and impairing antioxidant defence mechanisms in the testis. Additionally, BLM treatment caused a marked decline in sperm motility, an increase in abnormal sperm rates and severe histopathological damage in testicular tissue. However, co-administration of HES significantly mitigated these adverse effects by improving oxidative balance, restoring sperm quality and reducing histopathological injuries. In conclusion, HES demonstrated potential in alleviating BLM-induced reproductive toxicity, suggesting its therapeutic role in protecting against chemotherapy-induced male infertility.</p>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monoclonal Antibodies During Breastfeeding—Challenges With Relative Infant Dose","authors":"Paulina Flis,&nbsp;Gro C. Havnen,&nbsp;Elisabet Nordmo,&nbsp;Annika Asplund,&nbsp;Eva Wikström","doi":"10.1111/bcpt.70112","DOIUrl":"https://doi.org/10.1111/bcpt.70112","url":null,"abstract":"","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145110694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of an Artificial Intelligence Powered Medication Risk Score Calculator Application","authors":"Ádám Bertalan,&nbsp;Viola Angyal,&nbsp;Péter Domján,&nbsp;Eva Aggerholm Sædder,&nbsp;Gyula Király,&nbsp;Lóránd Erdélyi,&nbsp;Nóra Gyimesi,&nbsp;Elek Dinya","doi":"10.1111/bcpt.70109","DOIUrl":"https://doi.org/10.1111/bcpt.70109","url":null,"abstract":"<p>The publication explores the development of the Augmented Medication Risk Score (AUGMERIS) calculator, a web application supported by artificial intelligence, designed to automate the evaluation of medication therapies with the Danish Medication Risk Score (MERIS) method. It is a tool that assesses drug combinations and kidney function in estimated glomerular filtration rate (eGFR), which helps clinical pharmacists identify high-risk patients. To overcome the problem of processing unstructured electronic health records (EHRs), a hybrid text processing model was created by combining rigorous algorithms and Generative Pre-trained Transformer (GPT) technology, which was integrated into a web application along with an automated risk calculation programme. Our objective was to develop and test a globally accessible calculator application with the validation of performance on poor-quality data. Despite the validation limitations, the text processing function serves the application satisfactorily. The AUGMERIS web app is built with Python 3 and shared globally by Streamlit. Volunteer testers from eight different countries performed a total of 383 trial calculations. The application has the potential to improve global pharmacotherapy by identifying patients requiring medication reviews. Its wider adoption might enhance patient safety and optimize treatments in a variety of healthcare systems.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70109","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145110692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using Relative Infant Dose to Assess Drug Exposure in Breastfed Infants","authors":"Olav Spigset","doi":"10.1111/bcpt.70116","DOIUrl":"https://doi.org/10.1111/bcpt.70116","url":null,"abstract":"&lt;p&gt;The use of relative infant dose (RID) as a measure of drug exposure in breastfed infants has gained popularity in recent years. This trend is largely due to the accessibility of RID data in the literature, as its calculation typically requires only breast milk sampling, thereby eliminating the need for venous blood sampling from the mother or the infant. Additionally, the existence of cut-off values distinguishing ‘safe’ maternal drug use from use that might not be safe for the infant makes it relatively easy to interpret. If these assumptions really hold true, RID could be viewed as a most valuable tool for guiding drug use in lactating mothers in clinical practice.&lt;/p&gt;&lt;p&gt;However, as Flis et al. highlight in this issue of BCPT [&lt;span&gt;1&lt;/span&gt;], there are important caveats. In their article, they demonstrate that RID values for monoclonal antibodies are often miscalculated. They also argue that, due to some specific properties of this drug class, RID may not be a suitable metric. This raises the question: Could this be a more general challenge?&lt;/p&gt;&lt;p&gt;For drugs administered daily, the process of RID calculation is relatively straightforward using the formula presented by Fris et al. [&lt;span&gt;1&lt;/span&gt;]. Nonetheless, pitfalls remain. Ideally, milk samples should be collected throughout the dosing interval at sufficient frequency to estimate the area under the concentration–time curve (AUC) in milk and thereby also the average drug concentration in milk. Relying on a single or a few samples near trough levels will underestimate RID, whereas sampling near peak concentrations (C&lt;sub&gt;max&lt;/sub&gt;) may lead to overestimation. For drugs with extended dosing intervals (e.g., weekly or monthly), the situation becomes more complex [&lt;span&gt;1&lt;/span&gt;], but still, the core principle remains, that is, using the average milk concentration over the dose interval derived from AUC data. If sampling is sparse but involves many subjects, population pharmacokinetic (PopPK) modelling is a valuable alternative to traditional AUC calculations [&lt;span&gt;2&lt;/span&gt;]. However, when frequent sampling is available, the two methods yield close to identical RID values, as illustrated in our studies on cetirizine [&lt;span&gt;3, 4&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;For drugs with active metabolites, these should be included in RID calculations, that is, the pharmacologically active infant dose comprises the sum of the parent compound and its active metabolite(s). Prodrugs present an even more complex challenge from a theoretical point of view, although inactive parent substances are most often not included in the calculations.&lt;/p&gt;&lt;p&gt;Milk sampling should take place during steady-state conditions, which means that at least five elimination half-lives should pass after initiating or adjusting treatment before sampling. Sampling prior to steady state will underestimate RID. This is particularly relevant for drugs with long half-lives, such as monoclonal antibodies, where this condition may more often not be met [&lt;span","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70116","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145110693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antidepressants Use Among Pregnant Women in Denmark From 2001 to 2023: A Population-Level Drug Utilization Study","authors":"Anne-Johanne Andersen,&nbsp;Kasper Nørlund Enevoldsen,&nbsp;Anne Sophie Enevoldsen,&nbsp;Erika B. Gram,&nbsp;Per Damkier","doi":"10.1111/bcpt.70105","DOIUrl":"10.1111/bcpt.70105","url":null,"abstract":"<p>We evaluated trends in antidepressant use among pregnant women in Denmark from 2001 to 2023, comparing them with a matched comparison group from the general population. Data from the Danish Health Data Authority were used to assess annual antidepressant prescription redemption rates per 1000 pregnancies, with a focus on total antidepressant use, selective serotonin reuptake inhibitors (SSRIs) and serotonin noradrenaline reuptake inhibitors (SNRIs). Antidepressant use among pregnant women increased fivefold in the study period. In the comparison group, use increased 2.3-fold. After a decline following 2011, antidepressant use among pregnant women began to rise again in 2019, driven primarily by sertraline, which accounted for 76% of prescription redemptions in 2023. Other drugs such as escitalopram, duloxetine, mirtazapine and amitriptyline showed modest increases, while the use of most other antidepressants declined or stabilized. This upward trend likely reflects the influence of updated clinical guidelines and greater clinical acceptance of antidepressant use during pregnancy. Our findings emphasize how prescribing practices are sensitive to shifts in public discourse and guideline revisions, highlighting the importance of ongoing pharmacovigilance in managing maternal mental health.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12441221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}