European Journal of Clinical Pharmacology最新文献

{"title":"Estimation of linezolid exposure in patients with hepatic impairment using machine learning based on a population pharmacokinetic model.","authors":"Ru Liao, Lihong Chen, Xiaoliang Cheng, Houli Li, Taotao Wang, Yalin Dong, Haiyan Dong","doi":"10.1007/s00228-024-03698-2","DOIUrl":"10.1007/s00228-024-03698-2","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the pharmacokinetic changes of linezolid in patients with hepatic impairment and to explore a method to predict linezolid exposure.</p><p><strong>Methods: </strong>Patients with hepatic impairment who received linezolid were recruited. A population pharmacokinetic model (PPK) was then built using NONMEM software. And based on the final model, virtual patients with rich concentration values was constructed through Monte Carlo simulations (MCS), which were used to build machine learning (ML) models to predict linezolid exposure levels. Finally, we investigated the risk factors for thrombocytopenia in patients included.</p><p><strong>Results: </strong>A PPK model with population typical values of 3.83 L/h and 34.1 L for clearance and volume of distribution was established, and the severe hepatic impairment was identified as a significant covariate of clearance. Then, we built a series of ML models to predict the area under 0 -24 h concentration-time curve (AUC_0-24) of linezolid based on virtual patients from MCS. The results showed that the Xgboost models showed the best predictive performance and were superior to the methods for estimating linezolid AUC_0-24 based on though concentration or daily dose. Finally, we found that baseline platelet count, linezolid AUC_0-24, and combination with fluoroquinolones were independent risk factors for thrombocytopenia, and based on this, we proposed a method for calculating the toxicity threshold of linezolid.</p><p><strong>Conclusion: </strong>In this study, we successfully constructed a PPK model for patients with hepatic impairment and used ML algorithm to estimate linezolid AUC_0-24 based on limited data. Finally, we provided a method to determine the toxicity threshold of linezolid.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140876181","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":"External validation of population pharmacokinetic models of tacrolimus in Thai adult liver transplant recipients.","authors":"Virunya Komenkul, Waroonrat Sukarnjanaset, Piyawat Komolmit, Thitima Wattanavijitkul","doi":"10.1007/s00228-024-03692-8","DOIUrl":"10.1007/s00228-024-03692-8","url":null,"abstract":"<p><strong>Objective: </strong>Several population pharmacokinetic models of tacrolimus in liver transplant patients were built, and their predictability was evaluated in their settings. However, the extrapolation in the prediction was unclear. This study aimed to evaluate the predictive performance of published tacrolimus models in adult liver transplant recipients using data from the Thai population as an external dataset.</p><p><strong>Methods: </strong>The selected published models were systematically searched and evaluated for their quality. The external dataset of patients who underwent the first liver transplant and received immediate-release tacrolimus was used to assess the predictive performance of each selected model. Trough concentrations between 3 and 6 months were retrospectively collected to evaluate the predictability of each model using prediction-based diagnostics, simulation-based diagnostics, and Bayesian forecasting.</p><p><strong>Results: </strong>Sixty-seven patients with 360 trough concentrations and eight selected published models were included in this study. None of the models met the predictive precision criteria in prediction-based diagnostics. Meanwhile, four published population pharmacokinetic models showed a normal distribution in NPDE testing. Regarding Bayesian forecasting, all models improved their forecasts with at least one prior information data point.</p><p><strong>Conclusion: </strong>Bayesian forecasting is more accurate and precise than other testing methods for predicting drug concentrations. However, none of the evaluated models provides satisfactory predictive performance for generalization to Thai liver transplant patients. This underscores the need for future research to develop population PK models tailored to the Thai population. Such efforts should consider the inclusion of nonlinear pharmacokinetics and region-specific factors, including genetic variability, to improve model accuracy and applicability.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140854034","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":"Drug administration via feeding tubes-a procedure that carries risks: systematic identification of critical factors based on commonly administered drugs in a cohort of stroke patients.","authors":"Jana Sommerfeldt, Hannes Sartorius, Bettina von Sarnowski, Sandra Klein, Christoph A Ritter","doi":"10.1007/s00228-024-03723-4","DOIUrl":"https://doi.org/10.1007/s00228-024-03723-4","url":null,"abstract":"<p><strong>Purpose: </strong>Drug administration via feeding tubes is considered a process with many uncertainties. This review aimed to give a comprehensive overview of data available on feeding tube application and to carry out risk assessments for drug substances commonly administered to stroke patients.</p><p><strong>Methods: </strong>Drugs frequently administered via feeding tubes were identified through a retrospective analysis of discharge letters from a stroke unit. Physicochemical, pharmacokinetic, and stability properties of these drugs and data on drug-enteral nutrition interactions were systematically searched for in the European Pharmacopoeia, Hagers Handbook of Pharmaceutical Practice, Birchers clinical-pharmacological data compilation, and the Martindale Complete Drug Reference, as well as from databases including DrugBank, DrugDex, PubChem, Google Scholar, and PubMed.</p><p><strong>Results: </strong>Of the drugs most commonly administered via feeding tubes in the present stroke patient cohort, bisoprolol, candesartan, and ramipril could be considered the least critical due to their overall favourable properties. Acetylsalicylic acid, amlodipine, hydrochlorothiazide, omeprazole and esomeprazole, simvastatin, and torasemide pose risks based on pH or light-dependent instability or proposed food effects. The most critical drugs to be administered via feeding tubes are considered to be furosemide, levodopa, and levothyroxine as they show relevant instabilities under administration conditions and substantial food effects; the latter two even possess a narrow therapeutic index. However, little information is available on drug-tube and drug-formula interactions.</p><p><strong>Conclusion: </strong>Feeding tube administration of medications turned out to be a highly complex process with several unmet risks. Therefore, investigations that systematically assess these risk factors using clinically relevant model systems are urgently needed.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787603","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":"Neuronal toxicity of monoclonal antibodies (mAbs): an analysis of post-marketing reports from FDA Adverse Event Reporting System (FAERS) safety database.","authors":"Nitin Kumar, Vivekanandan Kalaiselvan, Mandeep Kumar Arora","doi":"10.1007/s00228-024-03727-0","DOIUrl":"https://doi.org/10.1007/s00228-024-03727-0","url":null,"abstract":"<p><strong>Background: </strong>Monoclonal antibodies (mAbs) are pivotal in treating various diseases, including cancers and autoimmune disorders. Despite their therapeutic benefits, mAb therapy has been associated with neurological toxicity.</p><p><strong>Objectives: </strong>This study aimed to assess the occurrence of neuronal toxicity associated with mAbs, utilizing data from the FDA Adverse Event Reporting System (FAERS) safety database. The study also sought to delineate the medical characteristics of the reported cases.</p><p><strong>Methods: </strong>A comprehensive analysis of neurological adverse events reported in the FAERS database was conducted, employing computational methodologies such as proportional relative risk (PRR), information component (IC₀₂₅), and chi-square (χ²). Individual case safety reports (ICSRs) pertaining to neurological disorders linked to mAbs from the date of first global marketing authorization until June 30, 2023, were meticulously examined.</p><p><strong>Results: </strong>The FAERS safety database contains 79,022 ICSRs linking mAbs to nervous system disorders. Rituximab, bevacizumab, denosumab, nivolumab, and trastuzumab were frequently cited. Reported adverse events include headache, peripheral neuropathy, dizziness, and cerebrovascular accident. Most ICSRs (85.81%) were serious, mainly affecting females (57.04%) with a 14.09% fatality rate. Panitumumab, atezolizumab, bevacizumab, and trastuzumab showed strong drug-event associations. Signal disproportionate reporting (SDR) analysis flagged myasthenia gravis, peripheral neuropathy, and neurotoxicity across multiple mAbs, suggesting potential signals.</p><p><strong>Conclusions: </strong>Interdisciplinary collaboration between oncologists and neurologists is crucial for safe mAb use. Our study enhances understanding of mAb neurological safety. Disproportionality signal analysis provides valuable evidence for risk mitigation.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141763966","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":"Author's reply to the letter to the editor: \"Effects of dapagliflozin and empagliflozin on 6‑min walk distance in heart failure with preserved and reduced ejection fraction: A systematic review and meta‑analysis of randomized controlled trials involving 2624 patients\".","authors":"Mohammad Tanashat, Almothana Manasrah, Mohamed Abouzid","doi":"10.1007/s00228-024-03733-2","DOIUrl":"https://doi.org/10.1007/s00228-024-03733-2","url":null,"abstract":"","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747797","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":"Letter to the editor: \"Effects of dapagliflozin and empagliflozin on 6-min walk distance in heart failure with preserved and reduced ejection fraction: a systematic review and meta-analysis of randomized controlled trials involving 2624 patients\".","authors":"Kazumasa Kotake, Kazuki Adachi, Yuki Nakano","doi":"10.1007/s00228-024-03731-4","DOIUrl":"https://doi.org/10.1007/s00228-024-03731-4","url":null,"abstract":"","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733757","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":"Management of enzyme de-induction in a woman with HIV on methadone maintenance switched from nevirapine- to bictegravir-based antiretroviral regimen.","authors":"Dario Cattaneo, Andrea Giacomelli, Giacomo Casalini, Anna Lisa Ridolfo, Cristina Gervasoni","doi":"10.1007/s00228-024-03681-x","DOIUrl":"10.1007/s00228-024-03681-x","url":null,"abstract":"","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140287235","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":"High refill-adherence to adalimumab is associated with low disease activity in patients with inflammatory bowel disease.","authors":"Esma H San, Angelique Egberts, Caroline W Th van Dijck-van Boetzelaer, Rachel L West, Erwin C Vasbinder","doi":"10.1007/s00228-024-03676-8","DOIUrl":"10.1007/s00228-024-03676-8","url":null,"abstract":"<p><strong>Purpose: </strong>Adalimumab has evolved to one of the more affordable first-line biologics for the treatment of inflammatory bowel disease (IBD), since its patent expired. However, poor adherence to adalimumab is a concern and may limit its effectiveness. It is plausible that good adherence improves treatment outcomes in IBD patients, but evidence is scarce. The aim of this study was to assess whether high refill-adherence (medication possession ratio (MPR) ≥ 80%) to adalimumab is associated with less active disease in IBD patients.</p><p><strong>Methods: </strong>In this retrospective study, the MPR was used to assess refill-adherence of IBD patients using adalimumab. Disease activity was defined as a composite endpoint determined by endoscopy findings, laboratory results, validated questionnaires and clinical assessment by a gastroenterologist. Logistic regression was used to determine the association between high refill-adherence (MPR ≥ 80%) and disease activity.</p><p><strong>Results: </strong>IBD was in remission in 72 of the 113 included patients and 41 had active disease at the time of the most recent prescription. Out of the patients who were in remission, 86.1% were adherent vs. 75.6% in patients with active disease. High refill-adherence was significantly associated with lower odds of active disease after adjustment for confounders: adjusted odds ratio 0.297, 95% confidence interval 0.099-0.892.</p><p><strong>Conclusion: </strong>High refill-adherence to adalimumab therapy was associated with less active disease in IBD patients. Our results confirm the relevance of good adherence to adalimumab for achieving optimal treatment results, which may limit the need for switching to more expensive biologics.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140326469","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":"Is \"interventional trial\" a correct term to use in clinical research?","authors":"Rafael Dal-Ré","doi":"10.1007/s00228-024-03679-5","DOIUrl":"10.1007/s00228-024-03679-5","url":null,"abstract":"","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140329713","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":"Oral contraceptives in adolescents: a retrospective population-based study on blood pressure and metabolic dysregulation.","authors":"Priscila Xavier de Araújo, Priscila Moreira, Danilo Candido de Almeida, Alexandra Aparecida de Souza, Maria do Carmo Franco","doi":"10.1007/s00228-024-03671-z","DOIUrl":"10.1007/s00228-024-03671-z","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to explore the relationship between oral contraceptive use and blood pressure values and in a national cohort of women adolescents and to investigate the level of coexistence of the high blood pressure levels, dyslipidemia or insulin resistance.</p><p><strong>Methods: </strong>This is a retrospective cohort study that evaluated data form 14,299 adolescents aged 14 to 17 years. Crude and race-and age-adjusted analyses were performed using Poisson regression to estimate the prevalence ratios. Data clustering analysis was performed using machine learning approaches supported by an unsupervised neural network of self-organizing maps.</p><p><strong>Results: </strong>We found that 14.5% (n = 2076) of the women adolescents use oral contraceptives. Moreover, an increased prevalence of high blood pressure, dyslipidemia, and insulin resistance (all P < 0.001) was observed among adolescents who use oral contraceptives as compared to those who do not. Our analysis also showed that 2.3% of adolescents using oral contraceptives had both high blood pressure levels and dyslipidemia, whereas 3.2% had high blood pressure levels combined with insulin resistance (all P < 0.001). The algorithmic investigative approach demonstrated that total cholesterol, LDLc, HDLc, insulin, and HOMA-IR were the most predicted variables to assist classificatory association in the context of oral contraceptive use among women adolescents with high blood pressure.</p><p><strong>Conclusions: </strong>These findings suggest that oral contraceptives were associated with an increased prevalence of high blood pressure, dyslipidemia, and insulin resistance among women adolescents. Although the indication of this therapy is adequate to avoid unintended pregnancies, their use must be based on rigorous individual evaluation and under constant control of the cardiometabolic risk factors.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140329714","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}