Basic & Clinical Pharmacology & Toxicology最新文献

{"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}

{"title":"Recurrent Exposure to Amoxicillin Impairs Male Reproductive Function by Enhancing Oxidative Stress and DNA Fragmentation in the Testis of Swiss Albino Mice","authors":"Nabila Akhtara,&nbsp;Manuj Kr Bharali,&nbsp;Mrinmoy Chakraborty,&nbsp;Shilajit Parashar Thakur","doi":"10.1111/bcpt.70115","DOIUrl":"10.1111/bcpt.70115","url":null,"abstract":"<div>\u0000 \u0000 <p>The present study was designed to investigate the impact of recurrent exposure to amoxicillin on the male reproductive system by employing a multi-parametric approach in a mouse model. Animals (<i>n</i> = 20) were randomly assigned into two groups: Group I served as a negative control while Group II was treated with amoxicillin every alternative week for 10 weeks. At the end of the experiment period, five animals (<i>n</i> = 05) from each group were euthanised, blood and tissue samples were utilised for further analysis, and the remaining five (<i>n</i> = 05) animals per group were utilised to assess the fertility index. Ultrastructural and sperm parameter analyses and histomorphology assessment of the testis revealed significant impairments (<i>p</i> &lt; 0.05) following amoxicillin exposure. Amoxicillin exposure also caused significant elevation of oxidative stress and double strand DNA breaks in testicular cells as demonstrated by increased level of 8-OHdG and γ-H2AX positive cells in the testis (<i>p</i> &lt; 0.001). To summarise, this study indicated that recurrent exposure to amoxicillin can induce reproductive toxicity through oxidative stress and genotoxic mechanisms, compromising sperm integrity and fertility potential in male mice. This work highlights the need for evaluation of antibiotic safety concerning male reproductive health, with implications for clinical practice, environmental exposures and the development of strategies to mitigate fertility risks.</p>\u0000 </div>","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":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074314","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":"Retraction: Protection of Arsenic-Induced Hepatic Disorder by Arjunolic Acid","authors":"","doi":"10.1111/bcpt.70113","DOIUrl":"10.1111/bcpt.70113","url":null,"abstract":"<p><b>RETRACTION</b>: P. Manna, M. Sinha, and P. C. Sil, “Protection of Arsenic-Induced Hepatic Disorder by Arjunolic Acid,” <i>Basic &amp; Clinical Pharmacology &amp; Toxicology</i> 101, no. 5 (2007): 333–338, https://doi.org/10.1111/j.1742-7843.2007.00132.x.</p><p>The above article, published online on 3 September 2007 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editors-in-Chief, Jens Lykkesfeldt and Ulf Simonsen; the Nordic Association for the Publication of BCPT; and John Wiley &amp; Sons Ltd.</p><p>The retraction has been agreed following an investigation based on allegations raised by a third party. Figures 4A and 4C were found to be duplicates, and the authors were unable to provide the original data due to the age of the paper. Additionally, the article contains multiple scientific inaccuracies, conceptual flaws and methodological omissions. Thus, the editors consider the conclusions of this article to be invalid.</p><p>The authors disagree with the retraction.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70113","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068976","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":"The Effect of ABCB1 Polymorphisms on the Efficacy of Antidepressants","authors":"Sofie Voss Thorsen,&nbsp;Cille Bülow,&nbsp;Kim Dalhoff,&nbsp;David Peick Sonne","doi":"10.1111/bcpt.70097","DOIUrl":"10.1111/bcpt.70097","url":null,"abstract":"<p>This scoping review investigates the association between <i>ABCB1</i> polymorphisms and antidepressant efficacy in humans. A systematic search identified 630 records, of which 58 met the inclusion criteria, resulting in 42 unique studies (five randomised controlled trials (RCTs), two randomised studies (non-RCTs), 30 prospective cohort studies, three case–control studies, one cross-sectional clinical study and one phase I clinical trial). These studies examined single nucleotide polymorphisms (SNPs) in or near the <i>ABCB1</i> gene and their association with antidepressant treatment response. Of the 42 studies, 30 focused on rs1045642, the most extensively studied SNP. Among these, only 20% reported statistically significant associations. Beyond rs1045642, rs2032582 and rs1128503 were also frequently studied, but statistically significant associations were reported in only a minority of cases (28% and 13%, respectively), often with conflicting directions. Haplotype analyses involving all three SNPs (the TTT haplotype) showed mixed results. Results were variable across antidepressants, likely due to overlapping pharmacokinetic pathways. Methodological differences, including study design, sample sizes and definitions of remission, likely contribute to these inconsistencies. This review highlights the complexity of linking <i>ABCB1</i> polymorphisms to antidepressant treatment response and suggests the need for standardised methodologies and larger, diverse populations in future studies. Haplotype analyses could provide deeper insights and enhance personalised treatment strategies.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12436669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068944","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":"The Effects of Drugs on CYP3A Enzyme Activity and Protein Expression Through Ubiquitination Modification Regulation","authors":"Fang Wang,&nbsp;Xiwei Gu,&nbsp;Haiying Hong,&nbsp;Qianqian Xia,&nbsp;Yuxin Zhang,&nbsp;Ying Song,&nbsp;Baoxin Li,&nbsp;Pan Fan","doi":"10.1111/bcpt.70102","DOIUrl":"10.1111/bcpt.70102","url":null,"abstract":"<p>Cytochrome P450 3A4 (CYP3A4) is one of the most important members of the cytochrome P450 subfamily, which is involved in the catalytic process of many drug activation or deactivation. Meanwhile, it is also a risk factor for drug-induced toxic reactions. Our research investigates the impact of drugs on CYP3A4 enzyme activity and protein expression, and that CYP3A4 inhibition induced by drugs may exacerbate under hypoxia. Molecular docking has found that the drug has binding sites with amino acid residues in the active region of CYP3A4, which may affect the ability of the CYP3A4 enzyme to metabolize drugs. Twenty male Sprague Dawley rats were divided into two groups: control (FiO₂: 21%), hypoxia (FiO₂: 10%) for 14 days. Liver microsomes from hypoxic and normoxic rats were used for in vitro experiments by high-performance liquid chromatography. Drug concentration in blood in vivo was measured by LC–MS/MS. Further studies have revealed that drugs mediate the degradation of CYP3A4 ubiquitination-proteasome pathway through E3 ubiquitin ligase gp78 by immunoprecipitation, which may exacerbate the CYP3A4 inhibition under hypoxic conditions. These elucidated that the inhibition of CYP3A4 may worsen under pathological conditions (such as hypoxia), providing a basis for rational clinical medication to reduce or avoid drug interactions and toxic reactions.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12436983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068979","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":"How Is Psychotropic Use for Challenging Behaviour in People With Intellectual Disability Understood by Stakeholders? A Concept Analysis Using Rodgers' Evolutionary Approach","authors":"Dervla Kelly,&nbsp;Susan Morrissey,&nbsp;Darragh O'Regan,&nbsp;Drona Sharma,&nbsp;Owen Doody","doi":"10.1111/bcpt.70110","DOIUrl":"https://doi.org/10.1111/bcpt.70110","url":null,"abstract":"<p>Psychotropic use for challenging behaviours in people with intellectual disability persists despite initiatives and prescribing guidelines encouraging judicious use. The use of some medications, such as psychiatric medications, can be stigmatised or linked to certain social and cultural beliefs. Rodgers' (1989) evolutionary framework of concept analysis was employed, alongside qualitative data collection, to examine the extent to which people with intellectual disability, their family members and health professionals have similar beliefs about appropriate psychotropic use and shared decision making processes. This study found that the justification for psychotropic use ranges from maintaining mood and safety according to service users and service providers; however, only service providers spoke about the use of medication as a last resort or legacy use. We identified organisational and health system factors, as well as professional, cultural, and relational factors stemming from diverging perceptions of psychotropic risk and power imbalances that influence psychotropic use. This suggests that there are gaps in understanding how to support decision making among people with intellectual disability about their medications. The results clarify the need for further research on effective interventions to enhance the shared decision making process around medications.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70110","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038215","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}