British journal of clinical pharmacology最新文献

{"title":"Pharmacogenomic profiling of the efficacy of gemcitabine monotherapy in metastatic pancreatic cancer: Subgroup analysis of the GENESECT study","authors":"Takashi Yokokawa,&nbsp;Daiki Tsuji,&nbsp;Masahiro Hatori,&nbsp;Kazuyoshi Kawakami,&nbsp;Masahiko Nakao,&nbsp;Takuya Yano,&nbsp;Yuichiro Arakawa,&nbsp;Keisuke Matsuo,&nbsp;Yasukata Ohashi,&nbsp;Masato Ozaka,&nbsp;Naoki Sasahira,&nbsp;Yasuhiko Sakata,&nbsp;Yuki Kogure,&nbsp;Shinya Tamaki,&nbsp;Atsushi Wada,&nbsp;Yusuke Taki,&nbsp;Wataru Suzuki,&nbsp;Kazuo Kobayashi,&nbsp;Hiroshi Ishii,&nbsp;Kunihiko Itoh,&nbsp;Masakazu Yamaguchi,&nbsp;Kenichi Suzuki","doi":"10.1002/bcp.70611","DOIUrl":"10.1002/bcp.70611","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>In the GENESECT study, no significant gemcitabine (GEM) metabolism-related germline genetic polymorphisms (GPs) were identified because approximately 70% of patients received combination therapy with nab-paclitaxel, which has metabolic pathways different from GEM. The present study was a sub-analysis including only GEM monotherapy patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Of 159 patients analysed in the GENESECT study, only GEM-monotherapy patients were selected. The endpoints included carbohydrate antigen 19-9 (CA19-9) response (reduction ≥ 50% from the pretreatment level at 8 weeks), progression-free survival (PFS), and overall survival (OS) in relation to GPs. Analysed genes included those encoding GEM transporters and metabolic enzymes (<i>SLC29A1</i>, <i>ABCC5</i>, <i>CDA</i>, <i>DCK</i>, <i>RRM1/2</i>) and a tumour cell proliferation enzyme (<i>COX-2</i>). Screening and significance levels were set at 10% (univariable) and 5% (multivariable), respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Data for 50 patients were analysed. Genotype AA of <i>ABCC5</i> 1146A&gt;G (rs7636910) showed a higher CA19-9 response rate than AG/GG (52.9% vs. 21.2%, <i>p</i> = 0.023) and remained significant in multivariable analysis (odds ratio: 6.255, <i>p</i> = 0.014). It also tended to be associated with longer PFS, but not significantly (hazard ratio [HR]: 0.464, <i>p</i> = 0.074). By contrast, although CA19-9 responses were not significantly associated with <i>DCK</i> −1205T&gt;C (rs4694362), the TT/TC genotype was significantly associated with prolonged PFS compared with CC (median 127 vs. 48 days, <i>p</i> = 0.002), and this association remained significant in multivariable analysis (HR: 0.153, <i>p</i> = 0.028). No GPs were significantly associated with OS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p><i>ABCC5</i> and <i>DCK</i> might be related to the efficacy of GEM treatment, but further research is needed.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"92 10","pages":"3397-3406"},"PeriodicalIF":3.0,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bcp.70611","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148136846","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":"S. aureus colonization and clinical symptoms remain stable upon topical XZ.700 treatment: Results of a double-blind randomized clinical trial in patients with mild to moderate atopic dermatitis","authors":"Laura W. J. van der Meulen,&nbsp;Menthe E. Bergmans,&nbsp;Salma Assil,&nbsp;Naomi Klarenbeek,&nbsp;Marieke L. de Kam,&nbsp;Alexa J. Tibboel,&nbsp;Thorsten Brach,&nbsp;Bjorn L. Herpers,&nbsp;Johan Frieling,&nbsp;Vincent de Jong,&nbsp;Benthe Freyee,&nbsp;Martijn B. A. van Doorn,&nbsp;Robert Rissmann,&nbsp;Tessa Niemeyer–van der Kolk","doi":"10.1002/bcp.70630","DOIUrl":"10.1002/bcp.70630","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Recovering dysbiosis may improve atopic dermatitis (AD) symptoms. XZ.700 is a recombinant chimeric endolysin that specifically targets <i>Staphylococcus aureus</i> and could be a new treatment option for patients with AD. The aim of this first-in-human study was to evaluate the safety, tolerability and efficacy of topical XZ.700 and explore the pharmacodynamic effects in patients with mild to moderate AD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method and Materials</h3>\u0000 \u0000 <p>This study consisted of Part A and Part B. In Part A, subjects were randomized and received XZ.700 10 μg/g, XZ.700 30 μg/g, XZ.700 100 μg/g or vehicle twice daily for 7 days on nonlesional skin and on all lesions (1% ≤ BSA ≤ 10%). In Part B, subjects received XZ.700 100 μg/g or vehicle on all lesions twice daily for 14 days (1% ≤ BSA ≤ 15%). Clinical scores and patient-reported outcomes were recorded. Pharmacodynamic measurements were taken.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In total, 35 patients completed the study. Tolerability of XZ.700 was acceptable. XZ.700 100 μg/g showed no evidence of effect on cultured <i>S. aureus</i> (estimated difference −52.9% CFU/mL; 95% CI −88.4% to 90.8%), oSCORAD (1.03; 95% CI −5.20 to 7.26) or EASI (−0.534; 95% CI −2.48 to 1.41). Furthermore, XZ.700 treatment did not result in a significant reduction in the relative abundance of <i>S. aureus</i> via metagenomics or other pharmacodynamic outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Tolerability and safety of short-term topical administration of XZ.700 100 μg/g for 14 days were acceptable in most participants; however, some local application-site events occurred, and one hypersensitivity reaction led to discontinuation. XZ.700 did not demonstrate target engagement or clinical benefit <i>vs</i>. vehicle under the tested conditions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"92 10","pages":"3448-3459"},"PeriodicalIF":3.0,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bcp.70630","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148216609","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":"Comparative effectiveness and safety of proton pump inhibitors after myocardial infarction on dual antiplatelet therapy: Insights from a target trial emulation","authors":"Liang Zhao,&nbsp;Linjie Li,&nbsp;Chengcheng Wu,&nbsp;Hangkuan Liu,&nbsp;Geru Aa,&nbsp;Xiaozhi Chen,&nbsp;Zhiqiang Zhang,&nbsp;Nicholas W. S. Chew,&nbsp;Mark Y. Y. Chan,&nbsp;Ching-Hui Sia,&nbsp;Doreen Su-Yin Tan,&nbsp;Pengfei Sun,&nbsp;Xin Zhou,&nbsp;Qing Yang","doi":"10.1002/bcp.70650","DOIUrl":"10.1002/bcp.70650","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Current guidelines recommend co-prescribing proton pump inhibitors (PPIs) with dual antiplatelet therapy (DAPT) after acute myocardial infarction (MI) to prevent gastrointestinal bleeding. Emerging evidence indicates that PPIs have distinct pharmacokinetic profiles, and their cardiovascular and bleeding effects may not represent a class effect.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used electronic health record data from the Tianjin Health and Medical Data Platform to emulate target trials comparing effectiveness and safety of three commonly used PPIs in clinical practice. The effectiveness outcome was gastrointestinal bleeding, and the safety outcome was composite cardiovascular events. Cox proportional hazards model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) between individual PPIs. We further applied XGBoost-based prognostic models to assess treatment effect heterogeneity across strata of predicted baseline risk.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 51 072 MI patients on DAPT, 22 671 were prescribed rabeprazole, 18 081 pantoprazole and 10 320 lansoprazole. During 1 year of follow-up, both pantoprazole (HR, 1.05 [95% CI, 0.97–1.13]) and lansoprazole (HR, 0.99 [0.91–1.09]) showed comparable cardiovascular risk to rabeprazole, but pantoprazole was associated with an increased risk of recurrent MI (HR, 1.20 [1.07–1.35]). For gastrointestinal bleeding risk, lansoprazole showed lower risk (HR, 0.81 [0.70–0.93]) compared with rabeprazole. Results were robust in multiple sensitivity analyses, and treatment effect heterogeneity showed gastrointestinal benefits of lansoprazole increase with the rising baseline bleeding risk.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In patients with acute MI receiving DAPT, the three PPIs showed similar cardiovascular safety, while lansoprazole was associated with a lower risk of gastrointestinal bleeding. External validation is warranted to examine these findings.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"92 10","pages":"3466-3476"},"PeriodicalIF":3.0,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148270316","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":"Psilocybin as serotonergic therapy in epilepsy: Narrative review of potentials and limitations","authors":"Miguel Benjamin Cervera-Sanchez,&nbsp;Daniel San-Juan,&nbsp;Roberto Díaz-Peregrino,&nbsp;Evelin Zulema Camacho-Castillo,&nbsp;Sthefany Anahi Bringas-Ortiz,&nbsp;Christian Padilla-Cabezutd","doi":"10.1002/bcp.70690","DOIUrl":"10.1002/bcp.70690","url":null,"abstract":"<p>Psilocybin shows potential in neuropsychiatric disorders but has a complex relationship with epilepsy and seizures. We reviewed literature up to November 2025 to identify studies relevant to psilocybin's effects on seizures and epilepsy, including our research on serotonergic modulation. Core studies addressing the research question and supplementary mechanistic evidence were included for synthesis. Risk of bias (RoB) was assessed by study type; independent reviewers achieved strong agreement (unweighted Cohen's <i>κ</i> = 0.80, SE = 0.185; 99% CI 0.006–0.011; per cent agreement = 88.9%). Experimental models suggest psilocybin, through 5-hydroxytryptamine receptor 2A (5-T2A) activation, may confer antiseizure effects. Preclinical data support serotonergic modulation as a promising strategy. RoB assessment highlighted methodological challenges, suggesting cautious interpretation. Clinical evidence in neuropsychiatric populations shows no increased seizure risk under medical supervision. Psilocybin could serve as an adjunctive therapy via selective serotonergic modulation. However, conflicting evidence and concerns at high doses urge caution. Future animal studies and clinical trials must confirm psilocybin's safety and efficacy in the treatment of epilepsy.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"92 10","pages":"3316-3332"},"PeriodicalIF":3.0,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148547962","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":"Ibuprofen vs. acetaminophen for acute mild-to-moderate pain management: A systematic review and meta-analysis of safety with a focus on paediatric populations","authors":"Gian Luigi Marseglia,&nbsp;Paola Giovanna Marchisio,&nbsp;Gregorio Paolo Milani,&nbsp;Michele Miraglia del Giudice,&nbsp;Irene Schiavetti,&nbsp;Giorgio Ciprandi","doi":"10.1002/bcp.70693","DOIUrl":"10.1002/bcp.70693","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>The purpose of this study is to compare the safety of ibuprofen and acetaminophen (paracetamol) for acute mild-to-moderate pain in children and adolescents through a systematic review and meta-analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>PubMed, Scopus and Web of Science were searched from inception to May 2026 for randomized controlled trials (RCTs) in patients aged 0–18 years that reported safety outcomes. RCTs enrolling adult or mixed-age populations in acute pain settings were also considered eligible when paediatric-relevant safety data could be extracted. The review was conducted and reported in accordance with the PRISMA 2020 statement. Primary outcomes were total adverse events (AEs), gastrointestinal, renal, hepatic and bleeding events. The risk of bias was assessed using RoB 2. Random-effects meta-analyses were expressed as risk ratios (RR) with 95% confidence intervals (CI).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Fifteen studies (2847 patients) were included across postoperative pain, musculoskeletal trauma, orthodontic pain and emergency department settings, with follow-up ranging from single-dose assessments to 12 months. Three studies, including 937 participants, contributed to the primary meta-analysis of any adverse event. Ibuprofen was not associated with a statistically significant difference in the risk of any adverse event compared with acetaminophen (RR 0.80, 95% CI 0.36–1.79; <i>I</i>² = 2.9%). No serious renal or hepatic adverse events were reported.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Available RCT evidence did not show a clear difference in short-term safety between ibuprofen and acetaminophen in paediatric and acute pain populations; however, the certainty of the evidence is limited. Patient factors and clinical context should guide drug choice. Larger RCTs with standardized safety reporting are needed.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"92 10","pages":"3277-3287"},"PeriodicalIF":3.0,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148444382","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":"Impaired clopidogrel activation due to CYP2C19 phenoconversion after mild acute ischaemic stroke","authors":"Maryam Alaei,&nbsp;Hooshyar Honarmand,&nbsp;Mohammadreza Gheini,&nbsp;Ziba Gholipour,&nbsp;Yahia Bennani,&nbsp;Gelareh Banihashemi,&nbsp;Yalda H. Ardakani,&nbsp;Youssef Daali,&nbsp;Farhad Najmeddin","doi":"10.1002/bcp.70635","DOIUrl":"10.1002/bcp.70635","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Ischaemic stroke is a global health issue, and clopidogrel is widely used for secondary prevention and undergoes hepatic activation by cytochrome 2C19 (<i>CYP2C19</i>) into its active thiol metabolite (H4-clopi). Although genetic polymorphisms are key determinants of this process, inflammatory states, such as acute ischaemic stroke, may cause phenotype–genotype mismatch (phenoconversion) and temporarily reduce <i>CYP2C19</i> enzyme activity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>This pharmacokinetic study was performed in Iranian patients with mild acute ischaemic stroke (NIHSS ≤ 5) who were prescribed clopidogrel for 21 days. Genotyping was conducted by real-time PCR. <i>CYP2C19</i> activity and Clopidogrel metabolism were assessed in both the acute and post-acute phase (21 days after acute ischaemic stroke) by using the omeprazole metabolic ratio (MR) and the maximum plasma concentration (Cmax) of H4-clopi, respectively. Laboratory parameters and demographic characteristics were also recorded.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Thirty-three patients were enrolled (mean age 63 ± 10.5 years; 66% male). Genotype results were consistent with previous reports in ethnically matched healthy populations. <i>CYP2C19</i> activity was significantly reduced in the acute phase and recovered only partially in the post-acute phase. Regardless of genotype, H4-clopi Cmax was significantly lower in ischaemic stroke patients than in healthy controls in both phases, with no significant interphase improvement (<i>p</i> &lt; 0.05). Inflammatory markers and NIHSS scores significantly decreased in the post-acute phase (<i>p</i> &lt; 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings demonstrate that genotyping alone may be insufficient to identify poor metabolizers, highlighting the importance of direct measurement of <i>CYP2C19</i> activity and consideration of alternative antiplatelet approaches.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"92 10","pages":"3424-3436"},"PeriodicalIF":3.0,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148161766","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":"Exploring individualized crovalimab dosing in PNH through in silico modelling: Potential for improved convenience and cost efficiency","authors":"Mendy ter Avest,&nbsp;Simon E. Koele,&nbsp;Nicole C. A. J. van de Kar,&nbsp;Saskia M. C. Langemeijer,&nbsp;Rob ter Heine","doi":"10.1002/bcp.70651","DOIUrl":"10.1002/bcp.70651","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Paroxysmal nocturnal haemoglobinuria (PNH) is a rare, acquired haematopoietic stem cell disorder. Crovalimab, a complement C5-inhibitor, is approved for PNH and can be self-administered subcutaneously every 4 weeks, offering a more convenient route than intravenous C5-inhibitors. Since exposure often exceeds pharmacokinetic targets and varies with body weight, we aimed to explored individualized dosing of crovalimab using clinical trial simulations to optimize therapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We compared standard, weight-based and therapeutic drug monitoring (TDM)-guided regimens in treatment-naïve PNH patients over 52 weeks by means of clinical trial simulations based on the population pharmacokinetic model developed by the market authorization holder.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Maintenance-phase crovalimab concentrations were generally supratherapeutic with substantial variability. Weight-based dosing reduced this variability, while TDM-guided dosing further minimized it and allowed dose intervals to be prolonged in 24% of patients to a mean of 5.0 weeks, while maintaining exposure comparable to the standard regimen.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Individualized dosing of crovalimab may reduce exposure variability and enable less frequent dosing, supporting the feasibility of more flexible cost-effective and patient-tailored treatment regimens.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"92 10","pages":"3460-3465"},"PeriodicalIF":3.0,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bcp.70651","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148249299","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":"Methyldopa and the risk of peripartum depression—A nationwide registry-based study","authors":"Joachim Hjalde Halmsted Olsen,&nbsp;Jon Trærup Andersen","doi":"10.1002/bcp.70627","DOIUrl":"10.1002/bcp.70627","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>The aim of this study was to investigate the risk of maternal peripartum depression following treatment with methyldopa.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A nationwide cohort of pregnant women covering births from 1996 to 2009 was generated from nationwide registries through linkage by national person-specific health security numbers. The exposure of interest was filled prescriptions for methyldopa during pregnancy and puerperium, while filled prescriptions for labetalol or nifedipine, and no exposure were comparators. Outcomes were filled prescriptions for antidepressants or antipsychotics or admission to a psychiatric ward due to depression or psychosis. Follow-up was from conception to 6 months after delivery to assess the effect of exposure in both pregnancy and puerperium combined and from delivery to 6 months after delivery to assess the effect of exposure in the puerperium only. Risk of depression was assessed with Cox proportional hazards regression models, adjusted for propensity scores.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 745 661 pregnant women were included in the study cohort covering 3620 pregnant women with exposure to methyldopa. Peripartum depression occurred in 46 cases (1.3%) after exposure to methyldopa in pregnancy and puerperium and in 53 cases (1.3%) after exposure to labetalol/nifedipine (HR = 1.12 [95% CI 0.75–1.66]). With exposure restricted to the puerperium, women developed depression in 10 cases (0.7%) after methyldopa and in 20 cases (1.0%) after labetalol/nifedipine (HR = 0.69 [95% CI 0.32–1.48]).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Maternal use of methyldopa during pregnancy and puerperium was not associated with an increased risk of peripartum depression.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"92 10","pages":"3407-3412"},"PeriodicalIF":3.0,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148142720","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":"Evaluating the pharmacokinetics, efficacy and safety of low-dose cannabidiol","authors":"William George Warren,&nbsp;Myles Osborn,&nbsp;Andrew Yates,&nbsp;Saoirse Elizabeth O'Sullivan","doi":"10.1002/bcp.70691","DOIUrl":"10.1002/bcp.70691","url":null,"abstract":"<p>Use of non-prescription cannabidiol (CBD) has increased in recent years, with dose recommendations ranging from ~10 to 70 mg/day. To investigate this trend, many studies have utilized low-dose CBD paradigms in healthy volunteers and patient populations. Here, we review the pharmacokinetics (PK), pharmacodynamics (PDs), and safety of low-dose CBD (≤2.5 mg/kg or ≤175 mg/day). PK studies using low-dose, oral CBD (all included PK studies ≤150 mg) showed that peak (<i>C</i>_max) and total exposure (area under the curve [AUC]) were 5- to 100-fold lower than a typical 20 mg/kg dose of Epidiolex. PD studies showed very little evidence of physical or neurological effects of low-dose CBD in healthy volunteers. Drug–drug interactions (DDIs) with Δ9-tetrahydrocannabinol, amitriptyline, and hydromorphone were observed at low doses (10, 30, 50, 60, 100 mg), which may have implications for patients who are co-administering non-prescription CBD with other medications. In randomized controlled trials, there was no evidence that low-dose CBD ameliorated any of the endpoints measured in patients with Parkinson's, Crohn's, pain, fibromyalgia, stress, ocular hypertension or psoriasis. In sleep disorders (sleep duration, 160 mg), alcohol use disorder (alcohol craving and impaired control, 150 mg/day CBD + 0.41 mg/day THC) and multiple sclerosis (timed walk test and pain, 80 mg/day), CBD improved a small selection of endpoints, but consistent changes were not observed across related endpoints and trials. No studies reported serious adverse events associated with low-dose CBD, which was well tolerated. In conclusion, low doses of CBD show very little evidence of any biological effect or therapeutic value.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"92 10","pages":"3301-3315"},"PeriodicalIF":3.0,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148519984","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 voriconazole/posaconazole on CsA in paediatric allogeneic haematopoietic stem cell transplantation recipients: A real-world study","authors":"Meng-Meng Jia,&nbsp;Dao Wang,&nbsp;Jing Yang","doi":"10.1002/bcp.70609","DOIUrl":"10.1002/bcp.70609","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>The aim of this study is to investigate the key factors influencing the extent of DDI between cyclosporine A (CsA, GtoPdb Ligand ID: 2162) and voriconazole (VCZ, GtoPdb Ligand ID: 6424)/posaconazole (PCZ, GtoPdb Ligand ID: 6426) in Chinese paediatric allo-HSCT recipients and to establish evidence-based dose adjustment strategies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>One-hundred-four children were enrolled and already taking stable doses of oral CsA when voriconazole or posaconazole was initiated. Evaluate the CsA dose and body weight-adjusted dose-normalized concentration (C/D) required to achieve therapeutic trough concentration (Cmin) before and after initiation of voriconazole or posaconazole.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>CsA C/D increased by 173.37% during VCZ co-therapy and 132.90% during PCZ co-therapy. The magnitude of change in CsA C/D was significantly associated with <i>CYP2C19</i> (GtoPdb Enzyme ID: 1043) genotype and PCZ Cmin. For maintaining therapeutic CsA exposure, the required percentage reduction in CsA dose varied according to <i>CYP3A5</i> (GtoPdb Enzyme ID: 1040) genotype and age. In the VCZ group, dose reductions ranged from 22.22% to 43.47% across age and <i>CYP3A5</i> genotype subgroups. In the PCZ group, dose reductions ranged from 12.77% to 33.34% across corresponding subgroups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p><i>CYP2C19</i> genotype and PCZ Cmin independently affect the magnitude of the DDI between CsA and VCZ/PCZ in paediatric allo-HSCT patients, and <i>CYP3A5</i> genotype and age of children should be integrated to guide individualized CsA dose reduction when co-administered with VCZ or PCZ.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"92 10","pages":"3354-3364"},"PeriodicalIF":3.0,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148052784","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}