European Journal of Clinical Pharmacology最新文献

{"title":"Evaluation of the predictive performance of an online voriconazole dose calculator in children.","authors":"Abdullah Alsultan, Razan Almofada, Sufyan Alomair, Eric F Egelund, Ahmed A Albassam, Mohammed Ali, Charles A Peloquin, Khalid W Taher","doi":"10.1007/s00228-024-03762-x","DOIUrl":"10.1007/s00228-024-03762-x","url":null,"abstract":"<p><strong>Background: </strong>The dosing of voriconazole is challenging in pediatrics. One approach to improve the dosing is through the use of Bayesian concentration-guided dosing software. Our study assessed the predictive performance of a freely available online voriconazole dose calculator in pediatric patients \"NextDose\" ( https://www.nextdose.org/ ).</p><p><strong>Methods: </strong>Per each dose calculator, we predicted voriconazole concentrations. We did both a priori and a posteriori Bayesian predictions.</p><p><strong>Results: </strong>A total of 51 patients were included in this study. For a priori predictions, bias was + 26% while imprecision was 70%. For a posteriori predictions, bias and imprecision were 0.01% and 46%.</p><p><strong>Discussion: </strong>In conclusion, the available online dose calculator was overpredicting the concentrations before voriconazole observations were available. However, with just one measured concentration, the predictions improved with minimal bias and an acceptable level of imprecision. There is a need for more prospective studies evaluating the use of voriconazole dosing calculators in the pediatric population to assess if they can improve the achievement of therapeutic target concentrations compared to standard of care.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343999","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":"GLP 1 receptor agonists and obesity-associated cancers: a disproportionality analysis in Vigibase®.","authors":"Jean-Louis Montastruc","doi":"10.1007/s00228-024-03761-y","DOIUrl":"10.1007/s00228-024-03761-y","url":null,"abstract":"","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344000","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 \"Use of statins and risks of ovarian, uterine, and cervical diseases: a cohort study in the UK Biobank\".","authors":"Pei-Ying Chung, Kuan-Fu Liao, Shih-Wei Lai","doi":"10.1007/s00228-024-03760-z","DOIUrl":"10.1007/s00228-024-03760-z","url":null,"abstract":"","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Approaches for posaconazole therapeutic drug monitoring and their clinical benefits.","authors":"Silu Wang, Changkun Li, Yalin Dong, Weihua Dong","doi":"10.1007/s00228-024-03756-9","DOIUrl":"10.1007/s00228-024-03756-9","url":null,"abstract":"<p><strong>Objective: </strong>This review examines the progress of research on posaconazole therapeutic drug monitoring (TDM) that has focused on differences in the TDM of posaconazole after clinical application in different formulations and in different populations, the factors that affect posaconazole concentrations, the advantages of posaconazole TDM in terms of clinical efficacy and cost savings, and measurement methods.</p><p><strong>Methods: </strong>A literature search (2006 to 2024) was performed in PubMed and Embase with the following search terms: noxafil, posaconazole hydrate, posaconazole, drug monitoring, therapeutic drug monitoring, and TDM. Abstracts of review articles, prospective studies, and retrospective studies were reviewed.</p><p><strong>Results: </strong>TDM should be implemented earlier for posaconazole tablets and injections than for oral posaconazole suspensions. Posaconazole TDM is beneficial for improving clinical efficacy, and the incidence of breakthrough invasive fungal infections (IFIs) can be significantly reduced by gradually adjusting the posaconazole dose in response to TDM in patients with inadequate trough concentrations. Early TDM allows more patients to achieve target therapeutic posaconazole concentrations. TDM can also facilitate dose adjustments, which reduce the cost of this expensive drug. Different assay techniques, including chromatography, microbiological detection, chemofluorimetry, paper spray mass spectrometry, and capillary electrophoresis, can be used for posaconazole TDM.</p><p><strong>Conclusions: </strong>Posaconazole TDM has potential clinical utility and cost-saving benefits and could improve the outcomes of IFI treatment.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of age and renal function on the pharmacokinetics and protein binding characteristics of fludarabine in paediatric and adult patients undergoing allogeneic haematopoietic stem cell transplantation conditioning.","authors":"Christa E Nath, Sebastian P A Rosser, Kiran K Nath, Jason Chung, Stephen Larsen, John Gibson, Melissa Gabriel, Peter J Shaw, Steven J Keogh","doi":"10.1007/s00228-024-03751-0","DOIUrl":"10.1007/s00228-024-03751-0","url":null,"abstract":"<p><strong>Aim: </strong>To evaluate the population pharmacokinetics of unbound F-Ara-A (the circulating metabolite of fludarabine) in 211 patients (age range, 0.1-63.4 years) undergoing allogeneic haematopoietic stem cell transplantation conditioning.</p><p><strong>Methods: </strong>Total (n = 2480) and unbound (n = 1403) F-Ara-A concentrations were measured in blood samples collected at timed intervals after fludarabine doses ranging from 10 to 50 mg/m² and infused over 0.42-1.5 h. A three-compartment population pharmacokinetic model was developed based on unbound plasma concentrations and used to estimate F-Ara-A unbound pharmacokinetic parameters and fraction unbound (fu). A number of covariates, including glomerular filtration rate (GFR) and post-menstrual age (PMA), were evaluated for inclusion in the model.</p><p><strong>Results: </strong>The base population mean estimates ± relative standard error (%RSE) for unbound clearance from the central compartment (CLu) and inter-compartmental clearances (Q2u, Q3u) were 3.42 ± 3%, 6.54 ± 24% and 1.47 ± 16% L/h/70 kg, respectively. The population mean estimates (%RSE) for the unbound volume of distribution into the central (V1u) and peripheral compartments (V2u, V3u) were 9.65 ± 8%, 8.17 ± 9% and 16.4 ± 10% L/70 kg, respectively, and that for fu was 0.877 ± 1%. Covariate model development involved differentiating F-Ara-A CLu into non-renal (1.81 ± 9% L/h/70 kg) and renal components (1.02 ± 9%*GFR L/h/70 kg). A sigmoidal maturation factor was applied to renal CLu, with population mean estimates for the Hill exponent and PMA at 50% mature of 2.97 ± 4% and 69.1 ± 8% weeks, respectively.</p><p><strong>Conclusion: </strong>Patient age and GFR are predictors of unbound F-Ara-A CLu. This has the potential to impact dose requirements. Dose individualisation by target concentration intervention will be facilitated by this model once it is externally validated.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282330","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":"A critical review on approaches to generate and validate virtual population for physiologically based pharmacokinetic models: Methodologies, case studies and way forward.","authors":"Mahendra Chougule, Sivacharan Kollipara, Smritilekha Mondal, Tausif Ahmed","doi":"10.1007/s00228-024-03763-w","DOIUrl":"10.1007/s00228-024-03763-w","url":null,"abstract":"<p><strong>Purpose: </strong>In silico modeling and simulation techniques such as physiologically based pharmacokinetic (PBPK) and physiologically based biopharmaceutics modeling (PBBM) have demonstrated various applications in drug discovery and development. Virtual bioequivalence leverages these computation tools to predict bioequivalence between reference and test formulations thereby demonstrating possibilities to reduce human studies. A pre-requisite for virtual bioequivalence is development of validated virtual population that depicts the same variability as that of observed in clinic. This development, validation and optimization of virtual population is a key attribute of virtual bioequivalence based on which conclusion of bioequivalence is made.</p><p><strong>Methods: </strong>Various strategies for optimization of virtual population based on appropriate considerations of physicochemical, physiological and disposition aspects are demonstrated with the help of six diverse case studies of immediate and modified release formulations. Once the virtual population is optimized to match in vivo variability, it can be used for various applications such as biowaivers, dissolution specification justification, f2 mismatch, establishing dissolution safe space, etc. In this review article, we attempted to describe various methodologies and approaches for optimization of virtual population using Gastroplus.</p><p><strong>Results: </strong>Strategies based on optimization of virtual population with emphasis on specific and sensitive parameters were portrayed. We have further elucidated considerations related to study design, in vivo variability, sample size for optimization of virtual population from Gastroplus perspective.</p><p><strong>Conclusion: </strong>We believe that this review article provides a step-by-step process for virtual population optimization for interest of biopharmaceutics modeling scientists in order to ensure reliable and credible physiological models.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389013","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":"Olaparib-associated toxicity in cancer patients: a systematic review and meta-analysis.","authors":"Wenfang Jin, Qing Yang, Zhifeng Zhang, Jing Li","doi":"10.1007/s00228-024-03771-w","DOIUrl":"https://doi.org/10.1007/s00228-024-03771-w","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the characteristics of olaparib-associated adverse events (AEs) in cancer patients.</p><p><strong>Methods: </strong>Databases were searched for phase II and III randomized controlled trials (RCTs) involving olaparib treatment up to March 2024. A systematic assessment was performed.</p><p><strong>Results: </strong>Twenty-seven RCTs involving 9542 patients were included. This meta-analysis indicates that olaparib could significantly increase the risk of developing any all-grade (RR, 1.08; 95% CI, 1.03-1.13; p = 0.001) and high-grade (RR, 1.45; 95% CI, 1.19-1.77; p = 0.0003) AEs in cancer patients. Olaparib could increase the risk of dose reduction (RR, 3.00; 95% CI, 1.59-5.70; p = 0.0007) and treatment discontinuation (RR, 2.00; 95% CI, 1.28-3.14; p = 0.002). Hematologic toxicities and gastrointestinal toxicities commonly occur in patients receiving olaparib. Anemia, nausea, and fatigue were the most frequent AEs, with olaparib increasing the risk of both all-grade and high-grade occurrences of these events. Patients with longer treatment durations tend to have a higher risk of anemia. Patients with urinary system tumors tend to have a higher risk of nausea, while those with breast cancer tend to have a higher risk of fatigue. Olaparib maintenance therapy may be associated with a higher risk of fatigue. Olaparib could increase other AEs such as diarrhea, vomiting, decreased appetite, dyspepsia, dysgeusia, dizziness, headache, back pain, urinary tract infection, dyspnea, and cough.</p><p><strong>Conclusion: </strong>Olaparib-containing therapy could increase the occurrence of specific AEs in patients with cancer. Clinicians should be aware of these risks and conduct regular monitoring.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582088","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":"Serious gaming as potential training tool for recognition of adverse drug reactions: side-effect exposure-medical education (SeeMe).","authors":"Ingmar Bergs, Laura Bell, Sebastian Fedrowitz, Tim Krüger, Martin Lemos, Julia C Stingl, Katja S Just","doi":"10.1007/s00228-024-03739-w","DOIUrl":"10.1007/s00228-024-03739-w","url":null,"abstract":"<p><strong>Purpose: </strong>The recognition of adverse drug reactions (ADRs) is an important part of daily clinical work. However, medical education in this field is mostly drug-based and does not address adequately the complexity of this field regarding individual risk factors and polypharmacy. This study investigates the potential of the web-based serious game SeeMe (side-effect exposure-medical education) in pharmacological education of medical students to improve the recognition of relevant ADRs.</p><p><strong>Methods: </strong>One hundred fifty-seven medical students were recruited to evaluate the serious game SeeMe. SeeMe was developed to improve knowledge and recognition of ADRs in clinical practice. Players take on the role of a physician trying to understand fictional patients with ADRs. Before and after an 8-week playing period, an evaluation was carried out through a pre- and post-questionnaire and a pre- and post- knowledge test.</p><p><strong>Results: </strong>The students achieved significantly better results in the knowledge test, as almost twice as many exam-relevant questions were answered correctly (p < 0.001). The serious game had a positive effect on the students' perception of the importance of ADRs.</p><p><strong>Conclusion: </strong>This study demonstrates the potential of web- and case-based fictional serious games in medical education. The improved recognition of side effects represents a crucial step for education and training in clinical pharmacology. Future versions of the serious game may take this further and focus on training in the treatment of ADRs and their relevance in various healthcare professions.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11458730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999607","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":"Reference guides for the safe use of drugs during pregnancy: a systematic review and comparative analysis.","authors":"Xue-Feng Jiao, Panda Qiu, Zheyun Song, Xue Peng, Hailong Li, Linan Zeng, Lingli Zhang","doi":"10.1007/s00228-024-03736-z","DOIUrl":"10.1007/s00228-024-03736-z","url":null,"abstract":"<p><strong>Purpose: </strong>To comprehensively evaluate and compare all the available reference guides for the safe use of drugs during pregnancy, with the goal of determining the scientificity and reliability of these reference guides.</p><p><strong>Methods: </strong>We searched PubMed, EMbase, CNKI, Wanfang Database, and VIP database to comprehensively identify the available reference guides. Moreover, we selected 103 drugs based on relevant literatures, and compared the recommendations of each drug from different reference guides.</p><p><strong>Results: </strong>A total of 14 available reference guides were identified. However, none of these reference guides assessed the risk of bias of original studies or the quality of current evidence. Seven reference guides adopted expert consensus method to formulate pregnancy recommendations, while the rest reference guides did not report the formation method. Moreover, 77.7% of the selected drugs had inconsistent recommendations among different reference guides. In addition, the referenced human and animal studies for the same drug differed among different reference guides.</p><p><strong>Conclusion: </strong>Our results indicate that current reference guides for the safe use of drugs during pregnancy are less scientific and reliable, and there are considerable discrepancies in recommendations from different reference guides concerning drug use during pregnancy. The reasons for the discrepancies in recommendations include ① the literature search in most reference guides was not comprehensive, ② none of the available reference guides assessed the risk of bias of original studies or the quality of current evidence, and ③ the method adopted by current reference guides to formulate recommendations had obvious subjectivity and lacked of scientificity.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055258","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":"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":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11458809/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}