European Journal of Clinical Pharmacology最新文献

{"title":"Identification of the most cost-saving disease-modifying therapies and factors affecting the budget in the pharmacotherapy of multiple sclerosis: a systematic review.","authors":"Matin Jafari, Mehrshad Sebty, Shaghayegh Moradi, Hesam Noqani, Hadi Esmaily, Ghader Mohammadnezhad","doi":"10.1007/s00228-024-03783-6","DOIUrl":"10.1007/s00228-024-03783-6","url":null,"abstract":"<p><strong>Background: </strong>Multiple sclerosis (MS) is an immune-mediated disease that has a considerable health-related quality of life interference. Various disease-modifying therapies (DMTs) in MS management have been approved by the Food and Drug Administration or are currently used off-label. DMTs aim to slow down the progression of MS and decrease the frequency of relapses. This systematic review aimed to evaluate the budget impact of DMTs worldwide.</p><p><strong>Methods: </strong>A systematic search query was made to identify related articles in scientific databases. Eligible papers included their characteristics and model inputs, and results were extracted and reported. To critique the standard reporting of studies, a 32-item quality assessment checklist was used.</p><p><strong>Results: </strong>From 1865 records, 22 original budget-impact analyses (BIAs) were included. All BIAs were accepted in the quality assessment (Mean score: 84.4). The most used DMT was β-interferons and natalizumab among novel DMTs. The results of BIAs were highly sensitive to the route of administration, costs of side effects and administration, and presence of biosimilars. However, glatiramer acetate has not experienced significant discounts was the most reported budget-saving DMT.</p><p><strong>Conclusion: </strong>From the results, it can be concluded the budget impact of DMTs in managing symptoms and improving the quality of life of MS patients according to the setting included in the modeling and according to specific conditions and context is different and significantly affects the results of BIAs. For accurate predictions of the effects of DMTs on the distribution of budgets in the MS population, more specific BIAs with higher quality should be done.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":"247-267"},"PeriodicalIF":2.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767558","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 safety and effectiveness of tolvaptan in patients with heart failure and renal impairment: a systematic review and meta-analysis.","authors":"Aashish Kumar, Umer Iqbal, Shafin Bin Amin, Syed Ali Arsal, Syed Muhammad Sinaan Ali, Muhammad Ashir Shafique, Muhammad Saad Shahid, Aimen Naz, Emediong Santhus Asuka","doi":"10.1007/s00228-024-03778-3","DOIUrl":"10.1007/s00228-024-03778-3","url":null,"abstract":"<p><strong>Purpose: </strong>Patients with heart failure and concomitant renal impairment are often prescribed loop diuretics, such as furosemide, as the primary treatment. The present meta-analysis is focused on analyzing the safety and efficacy of the implementation of tolvaptan as a novel approach in patients with renal impairment and heart failure.</p><p><strong>Methods: </strong>Two reviewers conducted a screening of articles using online databases, including PubMed, Google Scholar, and Embase. Following a comprehensive literature search, seven articles that met all inclusion criteria (patients with heart failure and renal impairment) were selected for analysis. Subsequently, various primary and secondary outcomes were evaluated.</p><p><strong>Results: </strong>The primary outcomes of our study included urine volume, worsening renal function, blood urea nitrogen (BUN) levels, and creatinine levels. Tolvaptan demonstrated superior efficacy in increasing urine output with a standardized mean difference of 2.18 (95% CI 0.62-3.75, p = 0.006) and resulted in a lower incidence of worsening renal function with odds ratio 0.41 (95% CI 0.22-0.77, p = 0.006). Additionally, there was no significant difference in the tolvaptan and conventional treatment groups in changing serum creatinine levels with a standardized mean difference of - 0.37 (95% CI - 0.86 to 0.12, p = 0.135), but tolvaptan tends to decrease blood urea nitrogen levels with a standardized mean difference - 0.18 (95% CI - 0.30 to - 0.06, p = 0.004) in comparison to conventional treatment group.</p><p><strong>Conclusion: </strong>While tolvaptan administration was related to better renal outcomes, unresolved heterogeneities and various factors could have influenced our findings. Further research is needed to evaluate the role of tolvaptan in the treatment of this patient population.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":"203-216"},"PeriodicalIF":2.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695413","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 quantity, reliability, transparency, reporting, and interpretation of pharmacovigilance signal detection studies in pregnancy: a meta-epidemiological study.","authors":"Xue-Feng Jiao, Zhengyang Zhang, Lixiong Gong, Shan Lan, Songzhen Zhang, Jiang Wang, Xiubi Chen, Qiang Wei, Hailong Li, Linan Zeng, Lu Han, Lingli Zhang","doi":"10.1007/s00228-024-03790-7","DOIUrl":"10.1007/s00228-024-03790-7","url":null,"abstract":"<p><strong>Purpose: </strong>To systematically review the characteristics of the available pharmacovigilance signal detection studies in pregnancy, and comprehensively assess the reliability, transparency, reporting, and interpretation of these studies.</p><p><strong>Methods: </strong>We searched five databases from inception to February 2024 to identify the available pharmacovigilance signal detection studies in pregnancy. We extracted three aspects of information (basic information, data processing modes, signal detection analyses) to assess the reliability, transparency, and reporting of each study. Moreover, we adopted the criteria of Mouffak et al.'s study to assess the misinterpretation of signal detection results in these studies.</p><p><strong>Results: </strong>A total of 33 pharmacovigilance signal detection studies in pregnancy were identified. Among them, there were great methodological heterogeneities in the data processing modes (restriction to the population, comparator, standardization of drug names and adverse event names, the assigned roles of drugs, counting unit, etc.) and signal detection analyses (signal detection method, sensitivity analysis, subgroup analysis, adjustment for confounding factors, etc.). Moreover, 13 (39%) studies had at least one type of inappropriate interpretation and/or extrapolation of signal detection results.</p><p><strong>Conclusion: </strong>Our results reveals that the quantity of pharmacovigilance signal detection studies in pregnancy is relatively limited. Furthermore, the reliability, transparency, reporting, and interpretation of the existing studies are less optimistic. The main issues existing in the available pharmacovigilance signal detection studies in pregnancy consist of two aspects: (1) great methodological heterogeneities exist in the data processing modes and signal detection analyses among different studies and (2) inappropriate interpretation and extrapolation of signal detection results are frequent.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":"309-319"},"PeriodicalIF":2.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846254","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":"Risk of hospital inpatient opioid overdose (RHINOO): a review of factors impacting naloxone administration in patients receiving opioids.","authors":"Heather Alban, Natasha Ireifej, John D'Alessandro, Garrett Jordan, Ryan Lee, Nicholas Patricia, Jill Stoltzfus, Auguste Niyibizi","doi":"10.1007/s00228-025-03801-1","DOIUrl":"https://doi.org/10.1007/s00228-025-03801-1","url":null,"abstract":"<p><strong>Purpose: </strong>Opioid medications remain a common treatment for acute pain in hospitalized patients. This study aims to identify factors contributing to opioid overdose in the inpatient population, addressing the gap in data on which patients are at higher risk for opioid-related adverse events in the hospital setting.</p><p><strong>Methods: </strong>A retrospective chart review of inpatients receiving at least one opioid medication was performed at a large academic medical center from January 1, 2022, through December 31, 2022. Patients who received naloxone were designated as the overdose group, while those who received opioids without naloxone served as the control group. Suspected risk factors were included in a multivariable direct logistic regression model to identify patients at higher risk for opioid-related adverse events.</p><p><strong>Results: </strong>The review included 11,050 admitted patients who received an inpatient opioid, of whom 130 received naloxone. Analysis revealed that patients with creatinine clearance (CrCl) < 60 mL/min, co-administered benzodiazepine, body mass index (BMI) > 30 kg/m², underlying pulmonary disease, obstructive sleep apnea, chronic opioid use, and/or substance use disorder were at higher risk for requiring naloxone. These factors significantly influenced the likelihood and magnitude of in-hospital opioid overdose.</p><p><strong>Conclusion: </strong>These validated risk factors should be considered when administering opioid analgesics in the inpatient setting. Consideration should be given to reducing the dose and/or frequency of opioids in addition to the use of alternative analgesic modalities for patients with these risk factors to mitigate the risk of opioid-related adverse events. Incorporating these considerations into clinical practice can enhance patient safety and outcomes.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028327","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":"Grade ≥ 3 hematologic adverse events of immunotherapy in advanced NSCLC patients: a systematic review and meta-analysis.","authors":"Shuang Wang, Mengting Cai, Yajun Xiong, Tianyi Guo, Xiaoya Niu, Yu Chen, Yuying Feng, Chunhua Song, Aiguo Xu","doi":"10.1007/s00228-025-03803-z","DOIUrl":"https://doi.org/10.1007/s00228-025-03803-z","url":null,"abstract":"<p><strong>Background: </strong>The impact of incorporating immune checkpoint inhibitors (ICIs) into standard chemotherapy on the severity and risk of myelosuppression in advanced non-small cell lung cancer (NSCLC) patients remains uncertain.</p><p><strong>Methods: </strong>We conducted a systematic review and meta-analysis of phase 3 randomized controlled trials (RCTs) that evaluated ICIs in people with NSCLC. A comprehensive search of four databases, PubMed, Web of Science, Embase, and the Cochrane Library, was carried out from inception to 30 October 2023. Pooled analyses assessed the risk ratios (RR) for treatment-related hematological adverse events greater than or equal to grade 3. The protocol is registered with PROSPERO and has the CRD42024500056 registration number.</p><p><strong>Findings: </strong>Twenty-three phase 3 RCTs were contained, involving 15,844 people with NSCLC receiving ICIs with or without chemotherapy. Compared with chemotherapy alone, ICI monotherapy or dual immunotherapy reduced treatment-associated leukopenia (relative risk (RR) 0.03, 95% CI 0.01-0.08), neutropenia (RR 0.02, 95% CI 0.01-0.03), thrombocytopenia (RR 0.05, 95% CI 0.02-0.14), and anemia (RR 0.09, 95% CI 0.05-0.15), with a pooled incidence of 0.07%, 0.08%, 0.14%, and 9.07%. Compared with chemotherapy alone, ICIs in combination with chemotherapy increased the risk of developing treatment-related thrombocytopenia (RR 1.35, 95% CI 1.04-1.77), with a pooled incidence rate of 6.83%; it did not increase leukopenia (RR 0.97, 95% CI 0.70-1.35), neutropenia (RR 1.05, 95% CI 0.90-1.23), and anemia (RR 1.10, 95% CI 0.85-1.43), with pooled incidence rates of 4.47%, 14.67%, and 13.36%, respectively.</p><p><strong>Interpretation: </strong>For patients with advanced or metastatic NSCLC, severe hematological adverse events are uncommon when ICIs are used alone, as opposed to chemotherapy. However, when used in conjunction with chemotherapy, these side effects may be intensified, particularly in the form of an elevated incidence of thrombocytopenia of grade 3 or higher.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002517","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":"Safety profiles of fondaparinux in pregnant women: a systematic review and meta-analysis.","authors":"Dan Shan, Jinbiao Han, Yurou Ji, Yuexiao Wu, Ke Yi","doi":"10.1007/s00228-025-03804-y","DOIUrl":"https://doi.org/10.1007/s00228-025-03804-y","url":null,"abstract":"<p><strong>Background: </strong>The prevalence of conditions necessitating anticoagulation therapy among pregnant women has been steadily increasing. Although low-molecular-weight heparin (LMWH) is commonly used, several studies have investigated the use of fondaparinux in pregnant women. However, the safety profile of fondaparinux in this population remains to be fully elucidated.</p><p><strong>Methods: </strong>A comprehensive literature search across ten databases was conducted in September 2024. This meta-analysis was conducted following the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines for systematic reviews of observational studies. Dichotomous data from eligible studies were combined using the Mantel‒Haenszel model. Standard mean differences with 95% confidence intervals were assessed. Heterogeneity was evaluated using I² statistics and the Cochran Q test, and the quality of evidence was appraised using Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach.</p><p><strong>Results: </strong>Nine studies met the inclusion criteria. Based on the GRADE approach, the quality of evidence ranged from very low to low. Fondaparinux did not increase the incidence of bleeding-related adverse events (vaginal bleeding: OR = 0.99, 95% CI 0.43-2.30, P = 0.98; postpartum haemorrhage: OR = 0.35, 95% CI 0.07-1.73, P = 0.20). Fondaparinux was associated with reduced risks of hepatic transaminase elevation (OR = 0.20, 95% CI 0.08-0.49, P < 0.01), gastrointestinal reactions, allergies, and injection site skin reactions (OR = 0.19, 95% CI 0.09-0.41, P < 0.01).</p><p><strong>Conclusion: </strong>The findings of this systematic review and meta-analysis suggest that the use of fondaparinux among pregnant women has certain advantages. However, these conclusions warrant further validation through high-quality, large-scale studies conducted in multiple countries. (PROSPERO-CRD42024591579).</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002569","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":"Validating the accuracy of mathematical model-based pharmacogenomics dose prediction with real-world data.","authors":"Yolande Saab, Zahi Nakad","doi":"10.1007/s00228-025-03805-x","DOIUrl":"https://doi.org/10.1007/s00228-025-03805-x","url":null,"abstract":"<p><strong>Objective: </strong>The study aims to verify the usage of mathematical modeling in predicting patients' medication doses in association with their genotypes versus real-world data.</p><p><strong>Methods: </strong>The work relied on collecting, extracting, and using real-world data on dosing and patients' genotypes. Drug metabolizing enzymes, i.e., cytochrome CYP 450, were the focus. A total number of 1914 subjects from 26 studies were considered, and CYP2D6 and CYP2C19 gene polymorphisms were used for the verification.</p><p><strong>Results: </strong>Results show that the mathematical model was able to predict the reported optimal dosing of the values provided in the considered studies. Predicting patients' optimal doses circumvents trial and error in patients' treatments.</p><p><strong>Discussion: </strong>The authors discussed the advantages of using a mathematical model in patients' dosing and identified multiple issues that would hinder the usability of raw data in the future, especially in the era of artificial intelligence (AI). The authors recommend that researchers and healthcare professionals use simple descriptive metabolic activity terms for patients and use allele activity scores for drug dosing rather than phenotype/genotype classifications.</p><p><strong>Conclusion: </strong>The authors verified that a mathematical model could assist in providing data for better-informed decision-making in clinical settings and drug research and development.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002570","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 model of tranexamic acid in patients who undergo cardiac surgery with cardiopulmonary bypass.","authors":"Tsuyoshi Nakai, Takahiro Tamura, Yasuhiro Miyagawa, Takayuki Inagaki, Masato Mutsuga, Shigeki Yamada, Kiyofumi Yamada, Kimitoshi Nishiwaki, Hiroyuki Mizoguchi","doi":"10.1007/s00228-025-03802-0","DOIUrl":"https://doi.org/10.1007/s00228-025-03802-0","url":null,"abstract":"<p><strong>Purpose: </strong>Tranexamic acid (TXA) is widely used as an antifibrinolytic drug. However, studies to determine the optimal blood concentration of TXA have produced inconsistent results. During cardiac surgery, cardiopulmonary bypass (CPB) has serious effects on drug distribution, elimination, and plasma concentration. Therefore, we aimed to establish a population pharmacokinetics model of TXA in patients undergoing cardiac surgery with CPB that considers renal function as a covariate, thereby facilitating personalized treatment.</p><p><strong>Methods: </strong>In total, 453 TXA plasma samples were prospectively collected from 77 patients who underwent cardiac surgery with CPB. Plasma concentrations were determined by ultra-performance liquid chromatography-tandem mass spectrometry. The population pharmacokinetic model of TXA was analyzed using nonlinear mixed-effects modeling.</p><p><strong>Results: </strong>The two-compartment-based model with combined errors was determined as the best. The final model included the effect of bodyweight and CL_cr may be summarized as V₁ (L) = 12.77 × (bodyweight / 61.4)^0.911, V₂ (L) = 6.857, CL₁ (L/h) = 3.263 × [CL_cr (L/h) / 61.0]^0.752, CL₂ (L/h) = 2.859.</p><p><strong>Conclusion: </strong>Patients who undergo cardiac surgery with CPB may require an adjusted dose of TXA tailored to CPB due to lower CL₁ and increased V₁. Our TXA population pharmacokinetic model may be useful for developing individualized dosing designs for TXA in patients who undergo cardiac surgery with CPB.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002533","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":"Features and results availability of non-commercial Spanish COVID-19 trials: a systematic review of clinical trial registers and corresponding literature.","authors":"Rafael Dal-Ré, Elena García-Méndez, Ignacio Mahillo-Fernández","doi":"10.1007/s00228-024-03791-6","DOIUrl":"https://doi.org/10.1007/s00228-024-03791-6","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to characterize non-commercial Spanish COVID-19 trials and to determine the availability of results. Differences in outcomes according to the interventions assessed (medicines, non-medicines) will also be determined.</p><p><strong>Methods: </strong>This systematic review was conducted in March 2024 by searching non-commercial Spanish COVID-19 trials on four registers (EUCTR, Clinical.</p><p><strong>Trials: </strong>gov, ISRCTN, DRKS) and the WHO ICTRP. Phase-1 medicines trials were excluded. Several variables were retrieved from registers. Publication of main trial results were searched on PubMed, Cochrane COVID-19 Study Register, and Google Scholar. Journals' impact factor and articles' citations on Google Scholar were also registered. Results from medicines and non-medicines trials extracted from registers and articles were compared.</p><p><strong>Results: </strong>A total of 170 trials (57.1% medicines trials) were identified. These 170 trials were randomized (87.1%), masked (41.8%), or multicenter (39.4%); a total of 15,555 participants were enrolled, mostly in small trials (median, n = 88). Only 8.8% (15/170) of trials posted results on the registers; only 47.6% (81/170) of trials had either published results or posted them on registers. Publications accounted for 92.6% (75/81) of these. Articles were published in 56 different journals, had a median impact factor of 4.4 and a median of 10 citations. Most (58.7%, 44/75) described negative results. There were statistically significant differences (p < 0.001) between medicines and non-medicines trials on timely registration and on being multicenter. This was also the case among published trials with respect to negative results of the primary endpoint.</p><p><strong>Conclusion: </strong>Although most trials were randomized, a minority were multicenter, large, or masked. Trial results should be posted on the registers to make them accessible to everyone.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946734","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 pharmacokinetics of bedaquiline: a systematic review.","authors":"Jie Jin, Jie Cao, Ruoying Zhang, Lifang Zheng, Xinjun Cai, Jinmeng Li","doi":"10.1007/s00228-024-03788-1","DOIUrl":"https://doi.org/10.1007/s00228-024-03788-1","url":null,"abstract":"<p><strong>Background and objectives: </strong>Bedaquiline (BDQ) plays a critical role in the treatment of multidrug-resistant tuberculosis (MDR-TB). However, the large pharmacokinetic (PK) variability of BDQ presents a significant challenge in its clinical use. This study aimed to summarize the population PK characteristics of BDQ and to identify significant covariates affecting the PK variation of BDQ.</p><p><strong>Methods: </strong>The PubMed and Web of Science databases were systematically searched from their inception to October 1, 2023. Population pharmacokinetics (PPK) studies on BDQ were searched and identified in this review. The PK characteristics of included studies and the significant covariates were systematically summarized.</p><p><strong>Results: </strong>Eight studies conducted in adults and one in children and adolescents were included in this review. A three disposition compartments with dynamic absorption transport chamber model was the commonly used structural model for BDQ. Body weight, race, albumin, and concomitant medication were significant covariates affecting BDQ PK variation. With the increase of weight and albumin levels, the clearance (CL) of BDQ was gradually increased. The average CL value per body weight in children was 1.49-fold higher than that in adults. Black race patients had an 84% higher CL than other populations. Moreover, combined with rifampicin and rifapentine, BDQ had 378% and 296% higher clearance rates, respectively.</p><p><strong>Conclusions: </strong>Body weight, race, albumin level, and concomitant medication may be important factors affecting patients' exposure differences. Further PPK studies of BDQ are needed to facilitate optimal dosing regimens.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946740","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}