Clinical Pharmacokinetics最新文献

{"title":"Author's Reply to Helsby and Hannam: 'Understanding Voriconazole Metabolism: A Middle-Out Physiologically-Based Pharmacokinetic Modelling Framework Integrating In Vitro and Clinical Insights'.","authors":"Ayatallah Saleh, Josefine Schulz, Jan-Frederik Schlender, Linda B S Aulin, Amrei-Pauline Konrad, Franziska Kluwe, Gerd Mikus, Wilhelm Huisinga, Charlotte Kloft, Robin Michelet","doi":"10.1007/s40262-025-01553-w","DOIUrl":"10.1007/s40262-025-01553-w","url":null,"abstract":"","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":" ","pages":"1429-1431"},"PeriodicalIF":4.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12414042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on \"Understanding Voriconazole Metabolism: A Middle-Out Physiologically-Based Pharmacokinetic Modelling Framework Integrating In Vitro and Clinical Insights\".","authors":"Nuala A Helsby, Jacqueline A Hannam","doi":"10.1007/s40262-025-01554-9","DOIUrl":"10.1007/s40262-025-01554-9","url":null,"abstract":"","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":" ","pages":"1425-1427"},"PeriodicalIF":4.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Efsubaglutide Alfa on the Pharmacokinetics of Metformin and Digoxin in Healthy Participants.","authors":"Xiaojie Wu, Jinjie He, Junzhen Wu, Wei Liu, Yulong Xu, Yiming Li, Jing Zhang, Qinghua Wang","doi":"10.1007/s40262-025-01541-0","DOIUrl":"10.1007/s40262-025-01541-0","url":null,"abstract":"<p><strong>Background: </strong>Efsubaglutide alfa, as a novel glucagon-like peptide-1 receptor agonist, was developed for the treatment of type 2 diabetes mellitus. Its effect on the rate and extent of absorption of concomitant oral medications (digoxin and metformin) was evaluated in healthy participants.</p><p><strong>Methods: </strong>We conducted a single-center, open-label, fixed-sequence clinical trial involving 32 healthy participants who were assigned to either digoxin (N = 16) or metformin (N = 16) groups. The participants received oral doses of digoxin (0.25 mg, single dose) or metformin (1000 mg at first dose, 500 mg twice daily for 2 days) before and after subcutaneous injections of 3 mg efsubaglutide alfa at steady state. Pharmacokinetic parameters of digoxin and metformin before and after the administration of efsubaglutide alfa injections were measured, and safety assessments were conducted throughout the study.</p><p><strong>Results: </strong>Efsubaglutide alfa slightly delayed the time to reach peak plasma concentration (T_max) of digoxin but had no substantial effect on its elimination. While the maximum concentration (C_max) of digoxin decreased by approximately 24% (from 1.75 ± 0.673 to 1.37 ± 0.545 ng/mL), and AUC_0-inf increased by about 15% (from 20.2 ± 3.53 to 23.2 ± 4.04 ng/h/mL). In the metformin group, efsubaglutide alfa did not noticeably affect T_max, C_max,ss, or the overall pharmacokinetics, as demonstrated by a consistent AUC_0-tau (from 7557 ± 2155 to 8737 ± 2852 ng/h/mL). Adverse events with efsubaglutide alfa and co-administered medication were comparable to those reported during treatment with efsubaglutide alfa alone and were mostly gastrointestinal-related.</p><p><strong>Conclusions: </strong>No clinically significant pharmacokinetic change of digoxin and metformin was identified, and no new safety issues were observed with the co-administration of efsubaglutide alfa injection. These findings suggest that no dose adjustments are required for digoxin and metformin when co-administration with efsubaglutide alfa.</p><p><strong>Clinicaltrials: </strong></p><p><strong>Gov identifier: </strong>NCT05694221.</p>","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":" ","pages":"1367-1377"},"PeriodicalIF":4.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Population Pharmacokinetics and Pharmacodynamics Modeling for the Use of Recaticimab in Healthy Volunteers and Patients with Hypercholesterolemia.","authors":"Chang Shu, Ying Wang, Sheng Feng, Shengxian Yang, Kai Shen","doi":"10.1007/s40262-025-01512-5","DOIUrl":"10.1007/s40262-025-01512-5","url":null,"abstract":"<p><strong>Introduction: </strong>Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a protein secreted by the liver that binds to low-density lipoprotein (LDL) receptors, which leads to a decreased ability of the liver to clear LDL-C from circulation. By inhibiting PCSK9, it is possible to provide early intervention to achieve clinical benefits.</p><p><strong>Methods: </strong>The database was built using data derived from seven clinical studies, population pharmacokinetic/pharmacodynamic (PopPK/PD) and PK/PD analyses were conducted via nonlinear mixed effects analysis with NONMEM software. The parameter estimation of the model was performed using the first-order conditional estimation with interaction (FOCE-I) method. The stepwise covariate method (SCM) was used to develop and evaluate the final model.</p><p><strong>Results: </strong>A target-mediated drug disposition model (TMDD) model and an indirect response model were developed to illustrated the PopPK profile and PK/PD profile of recaticimab. The PopPK final model was described as a one-compartment TMDD model with a combined residual error model. The PopPK/PD final model was described as an indirect response model with an additive residual error model. Body weight, body mass index, age, statin therapy, and sex were introduced on the model as significant covariates.</p><p><strong>Discussion: </strong>No adjustment of clinical dosage is required based on the PopPK and PopPK/PD covariates. Estimated glomerular filtration rate and anti-drug antibodies are not significant covariates for any PopPK parameter. After achieving a steady state, switching the dosing regimen and prolonging the dosing interval should not cause concerns about drug efficacy.</p><p><strong>Trial registration: </strong>NCT03634436, NCT03944109, NCT05370950, NCT04455581, NCT04849000, NCT04885218, NCT04844125.</p>","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":" ","pages":"1341-1355"},"PeriodicalIF":4.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Paracetamol Concentrations and Time-Course of Ductus Arteriosus Diameter in Extremely Preterm Neonates: A Population Pharmacokinetic-Pharmacodynamic Analysis.","authors":"Faheemah Padavia, Jean-Marc Treluyer, Gilles Cambonie, Cyril Flamant, Aline Rideau, Manon Tauzin, Juliana Patkai, Géraldine Gascoin, Mirka Lumia, Outi Aikio, Frantz Foissac, Saïk Urien, Sihem Benaboud, Gabrielle Lui, Léo Froelicher Bournaud, Yi Zheng, Ruth Kemper, Marine Tortigue, Alban-Elouen Baruteau, Jaana Kallio, Mikko Hallman, Alpha Diallo, Léa Levoyer, Jean-Christophe Roze, Naïm Bouazza","doi":"10.1007/s40262-025-01567-4","DOIUrl":"https://doi.org/10.1007/s40262-025-01567-4","url":null,"abstract":"<p><strong>Background: </strong>Patent ductus arteriosus is a common complication of extreme prematurity. Prophylactic treatment with indomethacin or ibuprofen has shown efficacy on ductus closure but without reducing mortality and morbidity. Prophylactic treatment by paracetamol could be a safer alternative.</p><p><strong>Objective: </strong>The aim was to build a pharmacokinetic-pharmacodynamic (PKPD) model describing the effect of paracetamol on the time-course of the ductus arteriosus diameter.</p><p><strong>Methods: </strong>Extremely preterm neonates of 23-26 weeks of gestational age were recruited within 12 h after birth and were treated with prophylactic intravenous paracetamol for 5 days (two dose levels: 20 mg/kg followed by 7.5 mg/kg or 25 mg/kg followed by 10 mg/kg every 6 h). The diameter of ductus arteriosus was determined by echocardiography performed daily until day 7. The PKPD model was built using an I_max model with effect compartment and exponential disease progression model. Concentrations of paracetamol in the effect compartment were simulated with different doses over time for 500 virtual patients.</p><p><strong>Results: </strong>A total of 29 extremely preterm neonates with median birth weight of 800 g (IQR: 670-860) were included in the study. Between-subject variability was estimated on transfer rate constant between the central compartment and the effect compartment (ke₀) and maximum drug inhibition (I_max) parameters. Two subpopulations with different I_max values were identified: 99% for a first subpopulation of 10 patients and 42% for the second subpopulation of 19 patients. A negative effect of maximum fraction of inspired oxygen (FiO₂) used during transfer to intensive care unit and a positive effect of intubation and ventilation during treatment were significant on ke₀. Simulations showed that both dose levels generally enabled patients to reach the concentration needed to achieve 95% of maximal inhibition by the end of treatment. However, the second dose level enabled more than 90% of patients to reach this inhibition threshold as early as day one.</p><p><strong>Conclusion: </strong>The relationship between paracetamol and the time-course of ductus arteriosus diameter has been described in extremely preterm neonates. Intravenous paracetamol treatment with a loading dose of 25 mg/kg within 12 h after birth followed by 10 mg/kg every 6 h appears to be effective to accelerate time to ductus closure with limited benefit of a further dose increase.</p>","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Population Pharmacokinetic Model and Dosing Algorithm to Guide the Tacrolimus Starting and Follow-Up Dose in Living and Deceased Donor Kidney Transplant Recipients.","authors":"Marith I Francke, Sebastiaan D T Sassen, Nuria Lloberas, Helena Colom, Laure Elens, Serge Moudio, Aiko P J de Vries, Dirk Jan A R Moes, Ron H N van Schaik, Dennis A Hesselink, Brenda C M de Winter","doi":"10.1007/s40262-025-01533-0","DOIUrl":"10.1007/s40262-025-01533-0","url":null,"abstract":"<p><strong>Introduction: </strong>Tacrolimus treatment is complicated by its narrow therapeutic range and large inter- and intra-patient variability. This study aimed to develop a population pharmacokinetic model and dosing algorithm to predict an individual's dose requirement following living and deceased donor kidney transplantation.</p><p><strong>Methods: </strong>In this international, multicenter, retrospective study, data was collected from patients who had received a living or a deceased donor kidney and received tacrolimus twice daily. A population pharmacokinetic model was developed using nonlinear mixed-effects modeling (NONMEM).</p><p><strong>Results: </strong>This study included 13,427 tacrolimus concentrations from 1180 kidney transplant recipients. A two-compartment model with first-order absorption best described the data. The mean absorption rate was 6.59/h, apparent clearance 20.7 L/h, central volume of distribution 705 L, and peripheral volume of distribution 7670 L. Higher age, creatinine, and hematocrit, as well as lower height, were associated with lower tacrolimus clearance. Tacrolimus clearance was higher for cytochrome P450 (CYP) 3A5*1 carriers compared with CYP3A5*3/*3 individuals, and lower for CYP3A4*22 carriers compared with CYP3A4*1/*1 patients. Together, these covariates explained 19.3% of the inter-individual variability in clearance. From the full model, a starting dose algorithm was developed with age, height, and the CYP3A4 and CYP3A5 genotypes as covariates. Both the full model and the starting dose algorithm were successfully internally validated.</p><p><strong>Conclusions: </strong>In this international, multicenter study, age, CYP3A4 and CYP3A5 genotype, creatinine, height, and hematocrit were identified as significant covariates associated with tacrolimus pharmacokinetics, and can be used to predict the optimal individual's dose requirement for both living and deceased donor kidney transplant recipients.</p>","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":" ","pages":"1379-1394"},"PeriodicalIF":4.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12414073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revisiting Acyclovir Dosing for Adult Viral Encephalitis Using a Full Bayesian LeiCNS PBPK Modeling Approach.","authors":"Ming Sun, Martijn L Manson, Anne-Grete Märtson, Jacob Bodilsen, Elizabeth C M de Lange, Tingjie Guo","doi":"10.1007/s40262-025-01545-w","DOIUrl":"10.1007/s40262-025-01545-w","url":null,"abstract":"<p><strong>Background and objective: </strong>Acyclovir is a primary treatment for central nervous system (CNS) infections caused by herpes simplex virus (HSV) and varicella-zoster virus (VZV). However, patient outcomes remain suboptimal, despite acyclovir treatment. Given the lack of alternative therapies, there is a pressing clinical need to revisit acyclovir dosing for viral encephalitis. This study aimed to evaluate current and alternative acyclovir dosing regimens using a Bayesian CNS physiologically based pharmacokinetic (PBPK) modeling approach.</p><p><strong>Method: </strong>A full Bayesian analysis was performed using LeiCNS3.0 model to describe acyclovir's CNS distribution. Simulations were performed for standard dosing (10 mg/kg TID) and various alternative dosing regimens. Drug efficacy was evaluated using 50%fT > IC₅₀ (50% of the dosing interval with drug concentration above IC₅₀) and C_min > IC₅₀ (minimum concentration of the drug exceeding IC₅₀). A toxicity threshold of 25 mg/L for plasma peak concentration was applied.</p><p><strong>Results: </strong>The standard regimen (10 mg/kg TID) achieved the 50%fT > IC₅₀ target but failed to consistently meet the C_min > IC₅₀ target, particularly for VZV. Alternative regimens of increasing the dosing frequency to QID or extending infusion durations to 1.5 h or 2 h improved efficacy while maintaining safety. Prolonged infusion durations reduced peak plasma concentration thus lowered toxicity risks CONCLUSIONS: The Bayesian CNS PBPK modeling approach demonstrated robust predictive capacity for CNS PK. Current acyclovir dosing regimens may be inadequate for treating HSV and VZV encephalitis. Alternative dosing strategies involving increased frequency or extended infusion durations appear more effective and safer. Future efforts should focus on refining the PK/pharmacodynamic (PD) relationship between acyclovir exposure and antiviral efficacy to improve therapeutic outcomes.</p>","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":" ","pages":"1413-1423"},"PeriodicalIF":4.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12414069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel Approach to Evaluating the Design of Pediatric Pharmacokinetic Studies Focused on Accurate Dose Selection.","authors":"Yuanxi Zou, Jerry Nedelman, Mats O Karlsson, Elin M Svensson","doi":"10.1007/s40262-025-01542-z","DOIUrl":"10.1007/s40262-025-01542-z","url":null,"abstract":"<p><strong>Background and objective: </strong>In pediatric trial design, it is particularly essential to maximize data utilization and ensure robust designs while minimizing sample collection. A common criterion to justify pediatric pharmacokinetic study designs is based on parameter precision (PP) evaluation, recommended by the US Food and Drug Administration. Here, we propose an alternative approach to design evaluation based on accuracy for dose selection (ADS).</p><p><strong>Methods: </strong>This work was conducted using a simulation-and-reestimation framework, based on a real-case scenario of designing the single-dose pharmacokinetic study of the anti-tuberculosis (TB) drug pretomanid, with the aim of selecting doses for the next multidose long-term study. The study powers were computed using the ADS approach under scenarios with (1) real-case conditions, (2) high variabilities, (3) available options of tablet doses for selections. The study power using a PP approach was computed to compare with the ADS approach.</p><p><strong>Results: </strong>The ADS approach suggested that the design selected accurate doses with study power >80% in almost all dosing weight groups, whereas the PP approach found the design underpowered for clearance. The ADS-based power was decreased to ~65% in the smallest weight groups given high variability. Varying the options of dose levels affected the ADS-based power non-monotonically, although fewer levels generally yielded higher power.</p><p><strong>Conclusion: </strong>The ADS approach practically evaluates the precision in dose selection, providing a directly relevant decision criterion for designing pediatric pharmacokinetic studies and could be an alternative for power evaluation when the study is focused on determining doses using discrete tablet sizes.</p>","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":" ","pages":"1357-1365"},"PeriodicalIF":4.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12414038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Effect of Hepatic Impairment or Renal Impairment on the Pharmacokinetics of Aficamten.","authors":"Donghong Xu, Justin D Lutz, Punag Divanji, Jianlin Li, Youcef Benattia, Adrienne Griffith, Stephen B Heitner, Stuart Kupfer, Polina German","doi":"10.1007/s40262-025-01557-6","DOIUrl":"10.1007/s40262-025-01557-6","url":null,"abstract":"","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":" ","pages":"1433"},"PeriodicalIF":4.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12413999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics of Sufentanil After Epidural Administration During the Course of Extensive Abdominal Surgery.","authors":"Agnieszka Bienert, Agnieszka Borsuk-De Moor, Paulina Okuńska, Justyna Ber, Danuta Siluk, Małgorzata Waszczuk, Krzysztof Kusza, Tomasz Bartkowiak, Jakub Szrama, Anna Kluzik, Tomasz Koszel, Paweł Wiczling","doi":"10.1007/s40262-025-01543-y","DOIUrl":"10.1007/s40262-025-01543-y","url":null,"abstract":"<p><strong>Background and objective: </strong>Epidural sufentanil is widely used for intraoperative analgesia and is recognized as a safe and effective route of administration when carefully monitored and administered at the lowest effective doses. Optimizing drug dosing requires a precise understanding of its pharmacokinetics. While it is known that sufentanil concentrations in the blood decline more slowly after epidural administration compared with intravenous administration, and the flip-flop phenomenon has been observed in this context, a pharmacokinetic model accounting for this phenomenon has not yet been described.</p><p><strong>Methods: </strong>This study aimed to develop a pharmacokinetic model of sufentanil following epidural administration, with a focus on its absorption from the epidural space. The study was performed in 23 patients, aged 30-83 years with an American Society of Anesthesiologists (ASA) classification of 2-3, undergoing major abdominal (oncologic and non-oncologic) surgery under general anesthesia and epidural analgesia. Blood samples were collected, and sufentanil concentrations were measured at time points ensuring coverage of the absorption phase. Population analysis was performed using a full Bayesian approach implemented in Stan/Torsten programs with the \"cmdstanr\" and \"bbr.bayes\" packages in RStudio.</p><p><strong>Results: </strong>The Bayesian approach helped incorporate prior information about sufentanil disposition. A two-compartment disposition model with two-compartmental absorption best described the data, featuring a fast absorption rate constant into plasma and the peripheral compartment, and a slow redistribution process from the epidural fat compartment.</p><p><strong>Conclusions: </strong>This study mechanistically describes the flip-flop pharmacokinetics of sufentanil and allows for more precise dosing of epidural sufentanil (NCT06069219).</p>","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":" ","pages":"1331-1340"},"PeriodicalIF":4.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12414025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}