British journal of clinical pharmacology最新文献

{"title":"Phase 1, open-label, randomized study of the elecoglipron pharmacokinetic profile in healthy participants under fed and fasted conditions.","authors":"Jianfeng Xu, Amina Haggag, Laurie Butcher, Haihui Liu, Wen Chen, Xuefeng Sun, Aruni Jha, Hongtao Yu, Anis Khan, Victoria E R Parker, Christer Tannergren, Xiaoliang Pan, Jianfeng Xu, Jingye Zhou","doi":"10.1002/bcp.70852","DOIUrl":"https://doi.org/10.1002/bcp.70852","url":null,"abstract":"<p><strong>Aims: </strong>Elecoglipron (AZD5004/ECC5004) is an oral small-molecule glucagon-like peptide-1 receptor agonist (GLP-1 RA) in development for weight management in people living with obesity or overweight and type 2 diabetes. This study aimed to characterize the pharmacokinetics (PK) profiles of two formulations of elecoglipron under fed and fasted conditions.</p><p><strong>Methods: </strong>We assessed the PK profiles, safety and tolerability of two formulations of elecoglipron, 50 mg, under fed and fasted conditions in healthy participants in a phase 1, open-label, randomized, single-dose, fixed-sequence, crossover study.</p><p><strong>Results: </strong>Of 23 participants screened, 14 were randomized to elecoglipron and 13 (92.9%) completed the study. The half-life for both formulations under fasted and fed conditions ranged between 20.7 and 21.2 h. Between the fed (reference) and fasted groups, geometric mean ratios (GMR) and 90% confidence intervals (CI) for the F1 formulation: area under the plasma-concentration curve (AUC) from time zero to the last measurement (AUC_0-last) was 0.96 (0.82, 1.12), AUC from time zero extrapolated to infinity (AUC_0-inf) was 0.95 (0.82, 1.11), and maximum plasma concentration (C_max) was 1.15 (0.90, 1.46). Similar results were observed for F2 in the fed and fasted groups. Safety and tolerability were comparable for the two formulations. The most common AEs were gastrointestinal (nausea, vomiting, dyspepsia, abdominal discomfort) and mostly mild in severity.</p><p><strong>Conclusions: </strong>Elecoglipron demonstrated a PK profile supportive of once-daily dosing and may be administered under fed or fasted conditions. These findings support the continuing clinical development of elecoglipron. The trial is registered at ClinicalTrials.gov (NCT06268145). The trial was first registered on 20 February 2024.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223371","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":"Absorption, distribution, metabolism and excretion of londamocitinib after single-dose inhaled, intravenous and oral administration in healthy participants.","authors":"Camille Riff, Peter Bold, Maria Heijer, Ryan A Bragg, Danielle Steele, Tina Jellesmark Jensen, Davinder P S Dosanjh, Sabrina I Hanswijk-Bartelds, Esther van Duijn, Elwin R Verheij, Somasekhara Menakuru, Rod Hughes, Helena Dahlbäck","doi":"10.1002/bcp.70844","DOIUrl":"https://doi.org/10.1002/bcp.70844","url":null,"abstract":"<p><strong>Aim: </strong>Londamocitinib (AZD4604) is an inhaled, selective Janus kinase 1 (JAK1) inhibitor in development for asthma. This open-label, two-part, phase I clinical study (NCT06157255) used a radiolabelled microtracer approach to evaluate the absolute bioavailability and the absorption, distribution, metabolism and excretion (ADME) of inhaled londamocitinib after intravenous and oral administration in healthy male and female participants (n = 8).</p><p><strong>Methods: </strong>Pharmacokinetics, safety, metabolic profile and metabolite identification from plasma, urine, and faecal samples were assessed employing highly sensitive accelerator mass spectrometry. Participants received a single oral 4-mg dose of [¹⁴C]londamocitinib (NMT 37.0 kBq [¹⁴C]) in Part 1 and an intravenous 30-μg dose of [¹⁴C]londamocitinib (NMT 37.0 kBq [¹⁴C]), followed by a single inhaled dose of 3-mg londamocitinib in Part 2.</p><p><strong>Results: </strong>Mean recovery of total radioactive material after oral dosing was 76.3% in faeces and 8.7% in urine. After intravenous dosing, recovery was 67.3% in faeces and 16.0% in urine. Absolute bioavailability of oral londamocitinib was 40.4% and for inhaled administration was 62.5%. Unchanged londamocitinib constituted approximately 70% of circulating radioactivity in plasma and accounted for 47.8% and 28.4% of the administered dose in excreta after oral and intravenous administration respectively. No new safety signals were observed.</p><p><strong>Conclusion: </strong>Following inhaled and oral dosing, londamocitinib demonstrated rapid absorption, and faecal excretion as the principal route of elimination. Unchanged londamocitinib and metabolite M6 were the major entities present in plasma, urine and faeces. Londamocitinib, at these doses, exhibited an acceptable safety and tolerability profile.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223365","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":"Comment on 'Cefepime exposure in prolonged or intermittent infusion in critically ill children': An efficacy-toxicity target conflict.","authors":"Ercan Yılmaz","doi":"10.1002/bcp.70879","DOIUrl":"https://doi.org/10.1002/bcp.70879","url":null,"abstract":"","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149219882","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":"Systematic review of clinical trials and cohort studies evaluating HIV post-exposure prophylaxis (PEP) regimens to inform updated Canadian guidelines.","authors":"Stanley O Onyegbule, Maryam Habib, Rija Khalid, Jessie Tu, Deborah Yoong, Jaris Swidrovich, Wale Ajiboye, Patrick O'Byrne, Ameeta E Singh, Jean-Guy Baril, Tatiana Sotindjo, Mark W Hull, Darrell H S Tan","doi":"10.1002/bcp.70860","DOIUrl":"https://doi.org/10.1002/bcp.70860","url":null,"abstract":"<p><strong>Background: </strong>We conducted a systematic review of clinical trials and cohort studies on HIV post-exposure prophylaxis (PEP) regimens to inform updated 2025 Canadian guidelines.</p><p><strong>Methods: </strong>We searched Medline and Embase (July 2017-June 2024) for studies reporting on: HIV acquisition, PEP completion, adverse events (AEs) leading to discontinuation and/or moderate to severe adverse events. Two reviewers independently screened abstracts and publications and extracted data from eligible articles.</p><p><strong>Results: </strong>Of 5226 abstracts screened, we retrieved 112 full-text articles and included 22. Median study size was 160 (range = 52-26 988) participants. Regimens included DTG + TDF/XTC (n = 4, 18%), EVG/c/TDF/FTC (n = 4, 18%), BIC/TAF/FTC (n = 4, 18%), RAL + TDF/FTC (n = 4, 18%), EVG/c/TAF/FTC (n = 3, 14%), RPV/TDF/FTC (n = 2, 9%), DOR/TDF/FTC (n = 2, 9%), MVC + TDF/FTC (n = 1, 5%), a wide variety of protease inhibitor-based regimens (n = 7, 32%) and novel combinations with the injectable fusion inhibitor albuvirtide (n = 1, 5%); a third of studies included three or more regimens (n = 8, 36%). Among studies examining PEP completion rates (n = 12, 55%), cumulative completion rate was 86.6% (7779/8983 PEP episodes) and appeared highest for RAL + TDF/FTC, BIC/FTC/TAF and DOR/TDF/3TC at 96.4%, 96.3% and 95.0%, respectively. PEP tolerability was good, with few discontinuations due to adverse events; where data were available, this was lowest for INSTI-based regimens at 0.5% (pooled across two studies) for RAL + TDF/FTC, 1.0% (1/99) for DTG + TDF/XTC, 1.8% (2/109) for BIC/TAF/FTC and zero with albuvirtide (0/198). HIV seroconversions were rare (n = 5/8134, 0.06%) and often related to premature PEP discontinuation or repeated exposures.</p><p><strong>Conclusions: </strong>Multiple PEP regimens have been associated with high completion, good tolerability and rare seroconversion, supporting their inclusion in clinical guidelines.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206445","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":"Electronic prescribing: Implementation of a new approach to undergraduate teaching and assessment.","authors":"Hiten Mitha, Kurt Wilson, Jeanne Caffrey, Mini Singh, Harish Thampy","doi":"10.1002/bcp.70857","DOIUrl":"https://doi.org/10.1002/bcp.70857","url":null,"abstract":"<p><strong>Introduction: </strong>Electronic prescribing and medicines administration (ePMA) systems are increasingly used across UK healthcare to reduce medication errors and improve patient safety. Undergraduate medical curricula have traditionally relied on handwritten prescribing, creating misalignment between education and clinical practice. To address this, the University of Manchester introduced electronic prescribing using the British Pharmacological Society (BPS) platform across its undergraduate medical programme.</p><p><strong>Methods: </strong>This descriptive implementation (quality improvement) report outlines a curriculum change within a large undergraduate medical programme, structured using the ADDIE model. We describe the phased development and implementation of ePMA teaching and assessment using the BPS platform. Evaluation was quality improvement in orientation and included structured feedback from students, tutors and assessors; operational metrics including technical reliability, use of paper contingency processes and examiner staffing requirements; and assessment outputs including automated marking data, item-level performance and cohort-level examination observations used to support iterative refinement.</p><p><strong>Results: </strong>Feedback from staff supported the feasibility and acceptability of the approach. Operational data showed low reliance on paper contingencies and reduced examiner requirements (approximately 400 examiner hours annually) for prescribing Objective Structured Clinical Examinations. Automated marking and item-level assessment outputs identified common prescribing errors and informed refinements to subsequent teaching materials.</p><p><strong>Conclusion: </strong>This report describes the integration of the BPS platform into teaching and assessment within a large medical programme. Quality-improvement data suggest the approach was feasible to deliver at scale, aligned teaching and assessment closer with clinical practice and the Prescribing Safety Assessment and generated valuable data to support ongoing curriculum development and refinement.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179539","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":"From discrimination to transportability: Interpreting machine-learning prediction of antitubercular drug-induced liver injury.","authors":"Qing Yi, Kaifeng Han","doi":"10.1002/bcp.70890","DOIUrl":"https://doi.org/10.1002/bcp.70890","url":null,"abstract":"","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191245","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":"Interpreting 'similar outcomes' in a small real-world comparison of apixaban and vitamin K antagonists.","authors":"Fei Luo, Mingjie Shi","doi":"10.1002/bcp.70886","DOIUrl":"https://doi.org/10.1002/bcp.70886","url":null,"abstract":"","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165425","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":"Pharmacist's role in managing drug-drug interactions in people with HIV receiving antiretroviral therapy or HIV pre-exposure prophylaxis: A focus on polypharmacy and transitions of care in the United States.","authors":"Shawnalyn W Sunagawa, Elizabeth M Sherman, Melissa Badowski, David B Cluck, Spencer H Durham, Joshua P Havens, Emily Huesgen, Justin K Ma, Roxane Rohani, Eric G Sahloff, Kristy M Shaeer, Radhika S Polisetty","doi":"10.1002/bcp.70884","DOIUrl":"https://doi.org/10.1002/bcp.70884","url":null,"abstract":"","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient preferences for medicines information in cardiovascular disease and the influence of unmet needs on medication adherence: A cross-sectional study.","authors":"Lachlan L Dalli, Susie Cartledge, Caroline Trin, Zuhayr Alji, Justine Causing, Monique F Kilkenny, Antonia Arfaras, Stella Talic","doi":"10.1002/bcp.70867","DOIUrl":"https://doi.org/10.1002/bcp.70867","url":null,"abstract":"<p><p>Limited evidence exists on how patients with cardiovascular disease (CVD) prefer to receive medicines information and whether having unmet needs influences medication adherence. We conducted a cross-sectional study using national survey data (20/05/2025-25/06/2025) from Australian MedAdvisor application users taking ≥4 CVD medicines. The questionnaire covered demographics, medication adherence (MARS-5), and information needs and preferences. Multivariable linear regression examined associations between unmet information needs and adherence. Among 313 participants (mean age 68.5 years, 38.7% female), 52.4% reported unmet information needs, particularly on drug interactions and side effects/precautions. One third (31.9%) were completely adherent (MARS-5 25/25), while 49.2% were partially adherent (MARS-5 23-24). Most preferred receiving information via electronic messages (45%) or mobile applications (22%). After adjustment, unmet medicine information needs was associated with medication non-adherence (coefficient: -0.83 [95% CI: -1.22, -0.44]). These findings highlight a substantial need for improved medicines information, particularly via digital modalities, to enhance adherence in CVD.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164160","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":"Comparison of pooled and Bayesian approaches for the analysis of paediatric pharmacokinetic data leveraging prior adult knowledge: A simulation case study for monoclonal antibodies against soluble targets.","authors":"Misako Takenaka, Scott Marshall, Frances Stringer, Masanori Yamada, Chiara Zecchin","doi":"10.1002/bcp.70869","DOIUrl":"https://doi.org/10.1002/bcp.70869","url":null,"abstract":"<p><strong>Aims: </strong>Population pharmacokinetic (popPK) modelling is widely used to support paediatric dose optimization, yet consensus on appropriate modelling approaches remains limited. This study compared pooled and Bayesian popPK approaches for paediatric pharmacokinetics (PK) analysis using monoclonal antibody (mAb) examples.</p><p><strong>Methods: </strong>Paediatric and adult PK datasets were simulated using popPK models inspired by a published mepolizumab model, incorporating two clinically relevant scenarios reflecting different mechanisms of paediatric-adult mAb PK differences. Six paediatric study designs were evaluated. Paediatric PK was analysed using pooled and Bayesian approaches, and model performance was assessed based on absolute prediction error (PE) and precision of population and individual PK parameters.</p><p><strong>Results: </strong>When paediatric-adult PK differences were explained primarily by body size, pooled approach estimated paediatric population clearance more accurately (median absolute PE: 1.1%-1.2% with pooled approach vs. 4.1%-10.4% with the Bayesian approach) and was robust across study designs. In contrast, when age-related PK differences were present and paediatric sample size was small (≤ 30 subjects), the Bayesian approach provided more accurate population clearance estimates for 11-year-old population (median absolute PE: 3.4%-8.2% with the Bayesian approach vs.7.4%-15.7% with pooled approach). Individual exposure estimates were comparable between modelling approaches.</p><p><strong>Conclusions: </strong>In this case study based on mAbs acting on soluble targets, relative performance of pooled and Bayesian popPK approaches varied with the analysis objective, paediatric age group, ADME characteristics and paediatric study design. These findings provide practical considerations for applying pooled and Bayesian approaches in this context and may help inform the selection of popPK strategies to support model-informed paediatric dosing decisions.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149170035","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}