British journal of clinical pharmacology最新文献

{"title":"Developing the Inpatient Mental Health Pharmaceutical Assessment and Care Tool (IMPACT) for use by UK mental health pharmacy teams-a modified Delphi study.","authors":"Fatima Q Alshaikhmubarak, Richard N Keers, Petra Brown, Penny J Lewis","doi":"10.1002/bcp.70083","DOIUrl":"https://doi.org/10.1002/bcp.70083","url":null,"abstract":"<p><strong>Aims: </strong>To develop an evidence- and consensus-based patient prioritization tool for use by UK mental health inpatient pharmacy teams.</p><p><strong>Methods: </strong>A modified-Delphi technique was used to obtain experts' agreement on the content, design and practical use of the patient prioritization tool. Two sequential Delphi questionnaires were prepared based on published evidence concerning risk factors for drug-related problems in mental health hospitals and current prioritization practices used by UK mental health inpatient pharmacy teams. Questionnaires were discussed and agreed upon with a group of 5 stakeholders including 3 mental health pharmacy experts and 2 patient representatives. Pharmacy professionals, psychiatrists and academics were recruited through a previous study and professional networks. Agreement was achieved if ≥75 or ≥85% of the panel rated 6-7 or 5-7 in the Likert scale respectively.</p><p><strong>Results: </strong>In Delphi 1 questionnaire, 29 experts agreed to include 82 risk indicators in the tool and to categorize patients into 3 risk groups using a traffic light system (red = high-risk, amber = medium-risk, green = low-risk). In Delphi 2 questionnaire, 30 experts agreed on 13 statements guiding practical use of the tool and the preferred frequency of review was every 1-2 day for the high-risk group, every 2-4 days for the medium-risk group and once every working week for the low-risk group.</p><p><strong>Conclusion: </strong>This study developed the Inpatient Mental Health Pharmaceutical Assessment and Care Tool (IMPACT) for use by UK mental health pharmacy teams. Feasibility and acceptability testing should be carried out to refine the tool and support preparations for formal evaluation of its impact on patient care and service delivery.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126731","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 pharmacokinetic modelling of prednisolone in systemic lupus erythematosus patients: Analysis of exposure and disease activity.","authors":"Naïm Bouazza, Michaela Semeraro, Gabrielle Lui, Léo Froelicher-Bournaud, Laure Choupeaux, Jean-Marc Treluyer, Sihem Benaboud, Joelle Terzic, Eric Hachulla, Philippe Remy, Jérôme Harambat, Alexandre Karras, Caroline Rousset-Rouviere, Anne Jolivot, Zahir Amoura, Eric Daugas, Aurélie Hummel, Rémi Salomon, Jean-Christophe Lega, Stéphane Decramer, Alexandre Belot, Delphine Gobert, Nathalie Costedoat-Chalumeau, Stanislas Faguer, Isabelle Melki, Noémie Jourde-Chiche, Brigitte Bader-Meunier","doi":"10.1002/bcp.70103","DOIUrl":"https://doi.org/10.1002/bcp.70103","url":null,"abstract":"<p><strong>Aims: </strong>Prednisone is a widely used glucocorticoid in the treatment of lupus, although its dosing is often determined empirically. Prednisolone, the active metabolite of prednisone, is found in its free form in the serum. The goal of this study was to develop a population pharmacokinetic model in patients with systemic lupus erythematosus (SLE) to forecast free prednisolone concentrations and its association with disease activity.</p><p><strong>Methods: </strong>A total of 66 active SLE patients (adults and children) were included, and followed up prospectively (242 observations available). Plasma prednisolone concentrations were assessed using liquid chromatography-mass spectrometry, and the data were analysed using Monolix software. The pharmacokinetic model was a one-compartment open model with absorption lag time representing the delay for both absorption and metabolism from inactive (prednisone) to active form (prednisolone). This model predicted free concentrations, which were then used to calculate total concentrations based on established binding constants.</p><p><strong>Results: </strong>Free prednisolone clearance (CLu/F) and volume of distribution (Vu/F) were scaled allometrically to body weight. The typical population estimates (95% confidence interval) were 54 (48-62) L/h/70 kg and 235 (203-274) L/70 kg, respectively. Additionally, the bioavailability parameter was found to decrease non-linearly with the dose. Prednisolone cumulative exposure was not different between patients who responded at 3 months and those who did not.</p><p><strong>Conclusions: </strong>Robust pharmacokinetic targets are not yet clearly defined regarding toxicity or efficacy and are warranted in order to make a valuable contribution to prednisolone therapeutic drug monitoring in the context of SLE.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144136005","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":"Educate to medicate: A clinical pharmacologist's perspective.","authors":"Robert Likic, Michael Rieder","doi":"10.1002/bcp.70110","DOIUrl":"https://doi.org/10.1002/bcp.70110","url":null,"abstract":"","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126732","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":"Relevance of selected pharmacogenetic polymorphisms to bleeding and thromboembolic risks in Chinese patients taking direct-acting oral anticoagulants.","authors":"Dongxu Wang, Yang An, Xiaoyue Zhou, Huaru Chai, Jiani Huo, Chunrong Li, Minghui Du, Dapeng Dai, Chuanbao Li, Hao Chen","doi":"10.1002/bcp.70078","DOIUrl":"https://doi.org/10.1002/bcp.70078","url":null,"abstract":"<p><strong>Aims: </strong>Gene polymorphisms play a critical role in the variability of plasma concentrations of direct-acting oral anticoagulants (DOACs). In this study, we aimed to investigate the effects of genetic variants on the clinical outcomes of Chinese patients treated with DOACs.</p><p><strong>Methods: </strong>The retrospective study recruited 720 patients with nonvalvular atrial fibrillation who were receiving dabigatran, rivaroxaban or edoxaban. Cox regression models were employed to compare the clinical outcomes between carriers and noncarriers of the key single nucleotide polymorphisms.</p><p><strong>Results: </strong>Results revealed that the CES1 rs2244613 C allele significantly reduced bleeding events in patients treated with dabigatran (adjusted hazard ratio 0.33, 95% confidence interval 0.13-0.85, P = .021). The carriage of ABCB1 rs1045642 T allele was associated with a lower risk of thromboembolism in rivaroxaban users (adjusted hazard ratio 0.19, 95% confidence interval 0.07-0.57, P = .003). Additionally, a trend toward statistical significance (P = .052) was observed between the SLCO1B1 rs4149056 C allele and bleeding risk among the edoxaban users.</p><p><strong>Conclusions: </strong>Our study showed that the CES1 rs2244613 and ABCB1 rs1045642 alleles were associated with outcome events in Chinese patients taking dabigatran and rivaroxaban, respectively. The findings could help predict clinical outcomes and develop personalized anticoagulation treatment strategies for Chinese patients taking DOACs.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118845","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":"Correction to \"Recommended approaches for integration of population pharmacokinetic modelling with precision dosing in clinical practice\".","authors":"","doi":"10.1002/bcp.70106","DOIUrl":"https://doi.org/10.1002/bcp.70106","url":null,"abstract":"","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118910","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":"Reply to: Methotrexate toxicity and glucarpidase: A call for dose optimization. Koppen A, et al. Br J Clin Pharmacol. 2025;91(5):1289-1292 doi:10.1002/bcp.70044.","authors":"Carmelo Rizzari, Stefan Schwartz","doi":"10.1002/bcp.70105","DOIUrl":"https://doi.org/10.1002/bcp.70105","url":null,"abstract":"","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109501","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":"Alterations of appetite-regulating hormones in risperidone treated children and adolescents-a post hoc analysis of the SPACe study.","authors":"Kajie Liang, Brenda C M de Winter, Rebecca A Hermans, Sanne M Kloosterboer, Susanne Kuckuck, Izgi Bayraktar, Liesbeth F C van Rossum, Manon H J Hillegers, Sander A A van den Berg, Birgit C P Koch, Bram Dierckx","doi":"10.1002/bcp.70095","DOIUrl":"https://doi.org/10.1002/bcp.70095","url":null,"abstract":"<p><p>Weight gain and metabolic disruptions are common in children and adolescents treated with antipsychotics, but the underlying mechanisms are unclear, complicating prevention and treatment. This study examines the impact of risperidone on appetite-regulating hormones (insulin, leptin and bioleptin) and their relationship to body weight changes over time. In a post hoc analysis, we evaluated the correlation of appetite-regulating hormones with BMI z-scores during treatment and at a 6-month follow-up. The sample consisted of 10 participants (80% male, median age 9.7 years). A significant increase in bioleptin (p < .05) and BMI z-scores was observed over the 6 month period. At baseline, HOMA-IR, insulin, leptin, and bioleptin were significantly correlated with the BMI z-score; however, these associations were no longer observed after 6 months of treatment. Additionally, higher risperidone exposure correlated with lower appetite-regulating hormone levels at the 6-month mark. These findings indicate that risperidone significantly affects appetite-regulating hormones in children and adolescents, potentially contributing to antipsychotic-induced weight gain.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109767","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":"Pharmacokinetics and pharmacodynamics of empagliflozin in paediatric patients aged 10-17 years with type 2 diabetes mellitus.","authors":"Juliane Rascher, Shen Cheng, Curtis Johnston, Sebastian Härtter, Wojtyniak Jan-Georg, Jan Marquard, Igor Tartakovsky, Lori M B Laffel","doi":"10.1002/bcp.70096","DOIUrl":"https://doi.org/10.1002/bcp.70096","url":null,"abstract":"<p><strong>Aims: </strong>To characterize the pharmacokinetics (PK) and PK/pharmacodynamics (PD) regarding glycosylated haemoglobin (HbA_1c) lowering using the paediatric data from DINAMO and to assess differences compared with adults.</p><p><strong>Methods: </strong>Population PK and PK/PD models previously developed for empagliflozin in adults and adolescents were re-estimated in a Bayesian framework. The PK model included 223 observations from 74 patients receiving empagliflozin 10 mg and 25 mg and the PK/PD model used 394 observations from 103 patients receiving empagliflozin (n = 52) or placebo (n = 51).</p><p><strong>Results: </strong>Empagliflozin PK was well described by a 2-compartment model with sequential zero-order and first-order absorption, with tested covariate effects of sex, age, race and estimated glomerular filtration rate on apparent clearance, and fixed allometric exponents on apparent clearance, apparent central volume of distribution, apparent intercompartmental clearance and apparent peripheral volume of distribution. Simulations of area under the curve at steady state (AUC_ss) demonstrated that adult and paediatric subjects exhibit similar AUC_ss. The PK/PD data were adequately described by a turnover model with disease progression and AUC_ss inhibiting the HbA_1c synthesis through an inhibitory maximum effect relationship. Simulations showed that the placebo-adjusted HbA_1c decrease at Week 26 in the paediatric population was larger than that in the adult population (-0.699 vs. -0.528%).</p><p><strong>Conclusion: </strong>A Bayesian estimation framework enabled the characterization of empagliflozin PK and PK/PD with a limited number of samples in paediatric patients aged 10-17 years. Overall, the results confirm 10 and 25 mg as the appropriate empagliflozin doses in paediatric patients aged 10-17 years with type 2 diabetes mellitus.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101545","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":"Association between ramelteon and 30-day mortality in ICU patients with COVID-19: A retrospective analysis of the MIMIC-IV database.","authors":"Yu Tian, Zai-Sheng Qin, Yun-Yang Han","doi":"10.1002/bcp.70099","DOIUrl":"https://doi.org/10.1002/bcp.70099","url":null,"abstract":"<p><strong>Aims: </strong>Melatonin may improve the prognosis of severe COVID-19 patients. However, the association between its analogue ramelteon and the survival outcomes of severe COVID-19 patients remains unclear. This retrospective study was conducted to investigate this knowledge gap.</p><p><strong>Methods: </strong>The data of COVID-19 patients admitted to the ICU were extracted from the Medical Information Mart for Intensive Care IV 3.0 database. Patients were categorized into the ramelteon group and the non-ramelteon group based on the corresponding treatment. The primary outcome was 30-day mortality. Subsequently, propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were employed to address confounding variables. Kaplan-Meier analysis, Cox proportional hazards regression and subgroup analyses were performed to evaluate the association between ramelteon exposure and survival outcomes.</p><p><strong>Results: </strong>This study included 607 unexposed patients and 459 exposed patients. Thirty-day mortality was 10.2% in the ramelteon group and 30.1% in the non-ramelteon group. Results from 301 patient pairs in the PSM cohort showed that ramelteon exposure was associated with significantly lower 30-day mortality (12.3% vs. 19.6%, P = 0.012). IPTW and Cox regression also supported this association (P < 0.05). Finally, subgroup analysis showed that invasive mechanically ventilated (IMV) patients on ramelteon may have a greater survival benefit (P interaction = 0.017).</p><p><strong>Conclusions: </strong>This study suggests an association between ramelteon exposure and lower 30-day mortality in ICU patients with COVID-19, particularly among those receiving IMV. However, given the retrospective design of this study, these findings should be interpreted as hypothesis-generating rather than definitive.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101540","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":"Randomized trial: Peppermint oil (menthol) pharmacokinetics in children and effects on gut motility in children with functional abdominal pain: 540 mg vs. 900 mg dose comparison.","authors":"Robert J Shulman, Bruno P Chumpitazi, Daniel Gonzalez, Uttam Garg, Salma Musaad, Jiali Wen, Gregory L Kearns","doi":"10.1002/bcp.70097","DOIUrl":"https://doi.org/10.1002/bcp.70097","url":null,"abstract":"<p><strong>Aims: </strong>There is a paucity of information on the pharmacokinetics (PK) and pharmacodynamics (PD) of menthol, the active ingredient in peppermint oil (PMO). We studied the PK of menthol (540 and 900 mg) in children and measured their effects on gut transit/contractility.</p><p><strong>Methods: </strong>Children 7-12 years of age with functional abdominal pain underwent wireless motility capsule (WMC) testing. One week later, they were randomized to 540 mg or 900 mg of oral enteric-coated PMO. Blood was sampled over 24 h to determine menthol PK. The WMC test was repeated while they took their respective dose (180 mg thrice or 180 mg five times daily) for a week.</p><p><strong>Results: </strong>Twenty-five children received 540 mg, and 15 received 900 mg (mean age 10.4 ± 1.1 years, 60% female). Peak plasma concentrations (C_max) were observed at approximately 2.5 h post-dose. There was no evident dose effect for the apparent elimination rate constant, time of peak plasma concentration (T_max), C_max, total plasma clearance, nor the apparent volume of distribution. Mean area under the plasma concentration vs. time curve (AUC) for the 900 mg PMO dose cohort was approximately 1.5-fold higher compared with the 540 mg dose; the difference disappeared correcting for dose. Colonic and whole bowel transit time were significantly positively correlated with menthol AUC. The 900 mg (vs. 540 mg) dose decreased colonic (P = 0.002) and whole gut (P = 0.02) contraction frequency.</p><p><strong>Conclusions: </strong>The PK of menthol derived from PMO demonstrates apparent dose-proportionality, and gut transit and contractility are associated with the systemic concentration of menthol.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101591","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}