British journal of clinical pharmacology最新文献

{"title":"Exposure to pseudoephedrine during pregnancy and major congenital malformations: Findings from a large population-based cohort of pregnancies","authors":"Saar Dor,&nbsp;Tal Michael,&nbsp;Yael Levi,&nbsp;Gali Pariente,&nbsp;Eitan Lunenfeld,&nbsp;Amalia Levy,&nbsp;Shira Birenstock-Cohen,&nbsp;Sharon Daniel","doi":"10.1111/bcp.70001","DOIUrl":"https://doi.org/10.1111/bcp.70001","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>The aim of this study was to assess the risk of major congenital malformations following first-trimester pseudoephedrine (PSE) exposure.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A population-based observational cohort study was conducted on pregnancies of women aged 15–49 years, insured by Clalit Health Services in southern Israel, who gave birth or had elective pregnancy terminations due to suspected fetal malformation at Soroka Medical Center (1999–2017). The study focused on Clarinase, a drug that contains a high dose of PSE (120 mg) and 5 mg of loratadine. Multivariable negative binomial regression models were used to evaluate the risk for major congenital malformations, adjusting for potential confounders.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 251 543 pregnancies, 313 (0.12%) were exposed to high-dose PSE in the first trimester. PSE exposure was not associated with major congenital malformations overall (adjusted relative risk [aRR] = 0.90, 95% confidence interval [CI] 0.558–1.45; <i>P</i> = 0.66) or by organ system (cardiovascular: aRR = 0.938, 95% CI 0.499–1.762; central nervous system: aRR = 0.618, 95% CI 0.086–4.451; musculoskeletal: aRR = 1.800, 95% CI 0.801–4.042; gastrointestinal: aRR = 1.013, 95% CI 0.142–7.241; genitourinary: aRR = 0.704, 95% CI 0.225–2.204).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>First-trimester PSE exposure was not an independent risk factor for major congenital malformations, either overall or by organ system.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"91 6","pages":"1834-1841"},"PeriodicalIF":3.1,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcp.70001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144171648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Best fit framework synthesis of qualitative studies on factors associated with medication nonadherence in people with type 2 diabetes using the COM-B model","authors":"Vivien Teo,&nbsp;John Weinman,&nbsp;Kai Zhen Yap","doi":"10.1111/bcp.70059","DOIUrl":"https://doi.org/10.1111/bcp.70059","url":null,"abstract":"<p>This review aimed to synthesize factors associated with medication nonadherence among people with type 2 diabetes (PwT2D), using the Capability, Opportunity, Motivation and Behaviour (COM-B) model as the a priori model.</p><p>Studies published between January 2014 and April 2024 were searched on five databases. Studies were included if they recruited PwT2D aged &gt;18 years, investigated factors associated with adherence to oral and/or nonoral medications for diabetes, used qualitative research methods, were conducted in a community setting, were in English language and had accessible full-text articles. Best fit framework synthesis was undertaken, which led to the development of a hypothesized COM-B variant model specific to medication nonadherence among PwT2D. Study quality was assessed using published criteria to evaluate whether the study was adequately reported.</p><p>Twenty-two studies were included. Factors were mapped onto the COM-B model: physical capability (e.g., difficulty injecting insulin independently), psychological capability (e.g., understanding about diabetes), physical opportunity (e.g., cost of medication), social opportunity (e.g., quality of communication and relationship with healthcare providers), automatic motivation (e.g., habit formation) and reflective motivation (e.g., perceived necessity and effectiveness of medications). Reflective motivation had the most themes, while physical capability only had one theme. Personality was a theme that could not be mapped onto the model. Interactions between some COM-B components (e.g., capability and motivation) were observed.</p><p>This theoretically grounded synthesis may facilitate future intervention development by formulating a programme theory and identifying behaviour change techniques to address the identified factors.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"91 6","pages":"1675-1691"},"PeriodicalIF":3.1,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcp.70059","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144171870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic modifications in drug-induced liver injury: A systematic review","authors":"Romina Lorena de los Santos-Fernández,&nbsp;Antonio Segovia-Zafra,&nbsp;Guillermo Paz-López,&nbsp;Gonzalo Matilla-Cabello,&nbsp;Hao Niu,&nbsp;Ismael Álvarez-Álvarez,&nbsp;Camilla Stephens,&nbsp;Andrés González-Jiménez,&nbsp;M. Isabel Lucena,&nbsp;Raúl J. Andrade,&nbsp;Inmaculada Medina-Cáliz","doi":"10.1111/bcp.70053","DOIUrl":"https://doi.org/10.1111/bcp.70053","url":null,"abstract":"<p>Genetic susceptibility has been identified in idiosyncratic drug-induced liver injury, a potentially severe adverse reaction towards drugs, herbal products and dietary supplements. However, its occurrence cannot be fully explained by the presence of genetic variants in specific genes, suggesting that other factors are involved. Drug-induced liver injury epigenetic signatures could help explain genetic regulatory mechanisms behind this disease and might provide disease biomarkers. This systematic review aims to analyse all available information on epigenetic risk association studies in drug-induced liver injury. The main inclusion criterion was population studies on idiosyncratic drug-induced liver injury with significant risk association analysis between drug-induced liver injury and an epigenetic regulation mechanism. Out of the 7 included articles, 6 focused on DNA methylation and 1 on long noncoding RNA. All of the studies were on antituberculosis drug-induced liver injury and came from Asia. CpG site methylation in the <i>CYP2D6</i> (odds ratio: 9.19, 95% confidence interval: 3.26–25.89, <i>P</i> &lt; .001) and <i>NAT2</i> (odds ratio: 8.37, 95% confidence interval: 2.39–29.32, <i>P</i> = .001) promoters conferred the highest risk. Hypomethylation of LINE-1 and Alu transposable elements has potential as antituberculosis drug-induced liver injury biomarkers, showing an area under the curve value of 0.94. To conclude, the studies mainly focused on DNA methylation modifications associated with antituberculosis drug-induced liver injury, with all of them coming from Asia, where tuberculosis is a public health burden. Despite the lack of knowledge in this area, the evidence has shown that DNA methylation alterations in antituberculosis drug-induced liver injury could have potential as a new diagnostic and therapeutic target.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"91 6","pages":"1660-1674"},"PeriodicalIF":3.1,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144171871","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":"Education about deprescribing for pre-licensed and licensed healthcare professionals: A scoping review","authors":"Brian J. Chow,&nbsp;Alexi M. Yuzwenko,&nbsp;Liz Dennett,&nbsp;Cheryl A. Sadowski","doi":"10.1111/bcp.70040","DOIUrl":"https://doi.org/10.1111/bcp.70040","url":null,"abstract":"<p>Deprescribing is complex because it involves patients' health, values, and preferences. The World Health Organization and Canadian Medication Appropriateness and Deprescribing Network have recommended that deprescribing be integrated into health curricula, prompting the need for further understanding about deprescribing education. The purpose of this research is to describe the literature regarding deprescribing education provided to healthcare professionals. We conducted a scoping review using the five-step model by Arksey and O'Malley with revisions from Levac et al. The databases searched included Medline, Scopus, Embase and ERIC. Papers were included if they were written in English and contained an educational intervention about deprescribing tailored toward physicians, pharmacists or nurses. White papers and conference abstracts were included. A total of 4853 abstracts were eligible for screening and 46 papers were included (25 full texts, 15 conference abstracts and 6 white papers). Thirty-three papers utilized group education for their intervention and of these, 20 involved interactive portions. Medicine was the most targeted profession, included in 29 papers. The most common outcomes were the number of medications deprescribed and an increase in learner knowledge and self-efficacy regarding deprescribing using self-assessment surveys or post-educational examinations. We found that there is evidence that educational interventions can increase participant knowledge regarding deprescribing and improve self-efficacy. To expand the education of deprescribing, future interventions should engage and utilize a variety of health professions and interventions could include real patients. Further research is required to determine the retention and application of deprescribing knowledge gained from single educational interventions.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"91 6","pages":"1649-1659"},"PeriodicalIF":3.1,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcp.70040","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144171599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Solanidine-derived CYP2D6 phenotyping elucidates phenoconversion in multimedicated geriatric patients","authors":"Jens Andreas Sarömba,&nbsp;Julian Peter Müller,&nbsp;Jolanta Tupiec,&nbsp;Anjali Roeth,&nbsp;Berkan Kurt,&nbsp;Florian Kahles,&nbsp;Thea Laurentius,&nbsp;Cornelius Bollheimer,&nbsp;Julia C. Stingl,&nbsp;Katja S. Just","doi":"10.1111/bcp.70004","DOIUrl":"https://doi.org/10.1111/bcp.70004","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Phenoconversion, a genotype-phenotype mismatch, challenges a successful implementation of personalized medicine. The aim of this study was to detect and determine phenoconversion using the solanidine metabolites 3,4-seco-solanidine-3,4-dioic acid (SSDA) and 4-OH-solanidine as diet-derived cytochrome P450 2D6 (CYP2D6) biomarkers in a geriatric, multimorbid cohort with high levels of polypharmacy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Blood samples and data of geriatric, multimedicated patients were collected during physician counsel (CT: NCT05247814). Solanidine and its metabolites were determined via liquid chromatography/tandem mass spectrometry and used for CYP2D6 phenotyping. CYP2D6 genotyping was performed and activity scores (AS) were assigned. Complete medication intake was assessed. A shift of the AS predicted via genotyping as measured by phenotyping was calculated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Solanidine and its metabolites were measured in 88 patients with complete documentation of drug use. Patients had a median age of 83 years (interquartile range [IQR] 77-87) and the majority (70.5%, n = 62) were female. Patients took a median of 15 (IQR 12-17) medications. The SSDA/solanidine metabolic ratio correlated significantly with the genotyping-derived AS (<i>P</i> &lt; .001) and clearly detected poor metabolizers. In the model adjusted for age, sex, Charlson Comorbidity Index and estimated glomerular filtration rate each additional CYP2D6 substrate/inhibitor significantly lowered the expected AS by 0.53 (95% confidence interval 0.85-0.21) points in patients encoding functional CYP2D6 variants (<i>R</i>² = 0.242).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Phenotyping of CYP2D6 activity by measurement of diet-derived biomarkers elucidates phenoconversion in geriatric patients. These results might serve as a prerequisite for the validation and establishment of a bedside method to measure CYP2D6 activity in multimorbid patients for successful application of personalized drug prescribing.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"91 6","pages":"1842-1852"},"PeriodicalIF":3.1,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcp.70004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144171864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on: ‘Effects of age, sex, daily dose, comorbidity and co-medication on venlafaxine-associated cardiovascular adverse events: A pharmacovigilance analysis of the FDA adverse event reporting system database’","authors":"Rikuto Masuda,&nbsp;Yoshihiro Noguchi,&nbsp;Ryo Kobayashi,&nbsp;Tomoaki Yoshimura","doi":"10.1111/bcp.70089","DOIUrl":"https://doi.org/10.1111/bcp.70089","url":null,"abstract":"","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"91 6","pages":"1873-1874"},"PeriodicalIF":3.1,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144171869","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 dosing of dispersible moxifloxacin formulation in children with rifampicin-resistant tuberculosis","authors":"Megan Palmer,&nbsp;Yuanxi Zou,&nbsp;Anneke C. Hesseling,&nbsp;Louvina van der Laan,&nbsp;Ingrid Courtney,&nbsp;Aarti A. Kinikar,&nbsp;Naresh Sonkawade,&nbsp;Mandar Paradkar,&nbsp;Vandana Kulkarni,&nbsp;Dessa Jean O. Casalme,&nbsp;Melchor V. G. Frias,&nbsp;Heather Draper,&nbsp;Lubbe Wiesner,&nbsp;Mats O. Karlsson,&nbsp;Paolo Denti,&nbsp;Elin M. Svensson,&nbsp;Anthony J. Garcia-Prats","doi":"10.1111/bcp.70005","DOIUrl":"https://doi.org/10.1111/bcp.70005","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Moxifloxacin is a priority drug for treating rifampicin-resistant tuberculosis (RR-TB). We assessed the pharmacokinetics of a child-friendly, dispersible 100 mg tablet moxifloxacin formulation (dispersed in water) compared to the standard 400 mg non-dispersible formulation (crushed and suspended in water) in children and evaluated current dosing recommendations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The CATALYST trial investigated the pharmacokinetics of moxifloxacin in children with RR-TB. Children were enrolled in South Africa, India and the Philippines. Intensive pharmacokinetic sampling was undertaken while children were taking the standard non-dispersible 400 mg moxifloxacin tablet formulation and repeated after switching to the novel dispersible formulation. Pharmacokinetic data were analysed using population pharmacokinetic modelling. Simulations were performed to evaluate moxifloxacin exposures in children compared to consensus adult reference exposures using current World Health Organization (WHO)-recommended doses and more recent model-based doses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Thirty-six children were enrolled [median age 4.8 (range 0.4–15) years and weight 15.6 (range 6.9–42.1) kg]. A two-compartment disposition model with first-order elimination and delayed absorption was developed. The bioavailability of dispersible versus standard formulations fulfilled standard bioequivalence criterion (ratio 1.05 with 90% confidence interval 0.95–1.15). Simulations showed WHO-recommended doses achieved exposures similar to those in adults in children &gt;10 kg, while children &lt;10 kg may require 33%–56% higher doses to reach adult reference exposures.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Dosing recommendations for children can be the same for the dispersible paediatric and standard non-dispersible adult moxifloxacin formulation. The current WHO dosing recommendation risks underdosing moxifloxacin in children &lt;10 kg. We propose optimized moxifloxacin doses for both formulations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"91 6","pages":"1853-1864"},"PeriodicalIF":3.1,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcp.70005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144171868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A systematic scoping review of metrics utilized to measure antibiotic consumption in hospital settings.","authors":"Marjan Kandimahforoujaki, Kiplin A Patanwala, Jan-Willem C Alffenaar, Asad E Patanwala","doi":"10.1002/bcp.70111","DOIUrl":"https://doi.org/10.1002/bcp.70111","url":null,"abstract":"<p><p>Antimicrobial stewardship (AMS) programs were introduced to promote the judicious use of antimicrobials and to combat antimicrobial resistance. Quantifying antibiotic consumption is an important part of AMS initiatives to achieve these objectives. However, various metrics are available for measuring antibiotic usage, each providing valuable insights but also possessing inherent limitations. The aim of this scoping review was to compare AMS metrics quantifying antibiotic consumption that have been evaluated within hospital settings. It examines the advantages, disadvantages, complexity and components of these metrics to inform their implementation. Four electronic databases, Medline, Embase, Web of Science and the Cochrane Library, were searched to identify articles, where two or more antibiotic consumption metrics were compared in the hospital setting. A total of 4874 articles were screened, with 21 selected for inclusion. The two most commonly used metrics (n = 19/21 studies) were defined daily dose (DDD) and days of therapy (DOT), which were compared to other metrics. DDD most likely overestimates antibiotic consumption for certain antibiotics such as beta-lactams and in certain settings such as the intensive care unit. Days of antibiotic spectrum coverage (DASC) and antibiotic spectrum index (ASI) are newer metrics that incorporate antibiotic spectrum and have been compared to DOT. DASC and ASI have shown low correlation with DOT. Reliance on a single metric such as DDD or DOT does not provide an accurate picture of antibiotic use. Hospitals should use DDD or DOT in combination with DASC or ASI to measure antibiotic consumption and the effectiveness of AMS programs.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172655","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":"Approaches to repurposing reverse transcriptase antivirals in cancer.","authors":"Richard Head, Saiful Islam, Jennifer H Martin","doi":"10.1002/bcp.70113","DOIUrl":"https://doi.org/10.1002/bcp.70113","url":null,"abstract":"<p><p>This review highlights the role of reverse transcriptase (RT) inhibition in cellular regulation associated with non-terminal repeat retrotransposons and endogenous retroviruses. Based on their pleiotropic characteristics, RT inhibitors (RTIs) are discussed as potential anticancer agents. Both the nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) display cytotoxicity in cancer cells which are likely mediated by endogenous RT inhibition and not necessarily by differing molecular structures. Three features of RTIs are evident in inducing cytotoxicity in cancer cells. Firstly, NRTIs and NNRTIs induce cell cycle arrest. Secondly, they suppress transposable elements, inhibit long interspersed nuclear elements (LINE)-1, with RTI key in cytotoxicity in cancer cells. Thirdly, the cyclic GMP-AMP-synthase-stimulator of interferon genes (cGAS-STING) pathway can be activated by LINE-1-derived cytoplasmic DNA with promotion of p21-dependent cell cycle arrest and cell-mediated immune response. This suggests that RTIs induce DNA strand breaks with incomplete retrotransposition, initiate cell cycle arrest and an immune response. Additionally, poly (ADP-ribose) polymerase 1 and 2 (PARP1, PARP2) and its relationship with DNA methylation is highlighted in the context of LINE-1 retrotransposition. There is a need to examine the relationship between PARP1, PARP2 and mutated BRCA proteins in normal and abnormal LINE-1 retrotransposition. This review explores how efavirenz and related RT inhibitors suppress endogenous reverse transcriptase, providing a basis for preclinical evaluation of RT inhibitors as potential repurposed drugs for cancer treatment.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156783","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 fate of thiopurine metabolites after switching to low-dose thiopurine with allopurinol or thioguanine in IBD patients: A retrospective analysis.","authors":"Ahmed B Bayoumy, Hedwig M A D'Agnolo, Nanne K H de Boer, Chris J J Mulder, Luc J J Derijks","doi":"10.1002/bcp.70112","DOIUrl":"https://doi.org/10.1002/bcp.70112","url":null,"abstract":"<p><strong>Aims: </strong>Shunting (hypermethylating) thiopurine metabolism, characterized by excessive 6-MMPR production and (sub)therapeutic 6-TGN levels, poses a significant challenge in the treatment of inflammatory bowel disease (IBD). This study evaluates the metabolic outcomes of switching to low-dose thiopurine with allopurinol (LDTA) or thioguanine (TG) in IBD patients with shunting metabolism.</p><p><strong>Methods: </strong>This retrospective study analysed demographic data, thiopurine metabolite profiles, and adverse event rates in shunting IBD patients before and after switching to LDTA or TG therapy. Metabolite variability was assessed by examining alterations in 6-MMPR and 6-TGN levels and their correlation before and after therapy switch.</p><p><strong>Results: </strong>Both therapies significantly reduced toxic 6-MMPR levels, with 100% of patients achieving non-toxic levels (6-MMPR-level below 7000 pmol/8 × 10E8 RBC) post-therapy. For TG, 93% of patients attained non-toxic 6-TGN levels (6-TGN < 1000 pmol/8 × 10E8 RBC). In contrast, LDTA showed greater variability in 6-TGN outcomes, with 50% of patients reaching therapeutic levels, 31% remaining subtherapeutic, and 19% within toxic range. The slope for LDTA was significantly positive (1.044, R² = 0.4515, P = 0.004), reflecting proportional increases in 6-TGN levels.</p><p><strong>Conclusions: </strong>Switching to LDTA or TG therapy in shunting IBD patients resulted in favourable alterations in thiopurine metabolism. However, LDTA appears to have a slightly less favourable metabolite profile, with some residual 6-MMPR formation and fewer patients achieving normal 6-TGN levels compared to TG. Given the challenges associated with achieving optimal thiopurine metabolite levels with LDTA and the need for closer monitoring of 6-TGN levels, TG appears a more suitable option for thiopurine shunting IBD patients.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149421","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}