Therapeutic Drug Monitoring最新文献

{"title":"Therapeutic Drug Monitoring of Immunosuppressive Drugs: A Field Constantly in Motion.","authors":"Maria Shipkova, Florian Lemaitre","doi":"10.1097/FTD.0000000000001286","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001286","url":null,"abstract":"","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":"47 1","pages":"1-3"},"PeriodicalIF":2.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142955382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Customizing Tacrolimus Dosing in Kidney Transplantation: Focus on Pharmacogenetics.","authors":"Nuria Lloberas, Anna Vidal-Alabró, Helena Colom","doi":"10.1097/FTD.0000000000001289","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001289","url":null,"abstract":"<p><strong>Abstract: </strong>Different polymorphisms in genes encoding metabolizing enzymes and drug transporters have been associated with tacrolimus pharmacokinetics. In particular, studies on CYP3A4 and CYP3A5, and their combined cluster have demonstrated their significance in adjusting tacrolimus dosing to minimize under- and overexposure thereby increasing the proportion of patients who achieve tacrolimus therapeutic target. Many factors influence the pharmacokinetics of tacrolimus, contributing to inter-patient variability affecting individual dosing requirements. On the other hand, the growing use of population pharmacokinetic models in solid organ transplantation, including different tacrolimus formulations, has facilitated the integration of pharmacogenetic data and other variables into algorithms to easier implement the personalized dose adjustment in transplant centers. The future of personalized medicine in transplantation lies in implementing these models in clinical practice, with pharmacogenetics as a key factor to account for the high inter-patient variability in tacrolimus exposure. To date, three clinical trials have validated the clinical application of these approaches. The aim of this review is to provide an overview of the current studies regarding the different population pharmacokinetic including pharmacogenetics and those translated to the clinical practice for individualizing tacrolimus dose adjustment in kidney transplantation.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":"47 1","pages":"141-151"},"PeriodicalIF":2.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142954014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New Developments and Therapeutic Drug Monitoring Options in Costimulatory Blockade in Solid Organ Transplantation: A Systematic Critical Review.","authors":"Gretchen N de Graav, Suwasin Udomkarnjananun, Carla C Baan, Marlies E J Reinders, Joke I Roodnat, Brenda C M de Winter, Dennis A Hesselink","doi":"10.1097/FTD.0000000000001275","DOIUrl":"10.1097/FTD.0000000000001275","url":null,"abstract":"<p><strong>Purpose: </strong>In this review, the authors summarized the latest developments in costimulatory blockade to prevent rejection after solid organ transplantation (SOT) and discussed possibilities for future research and the need for therapeutic drug monitoring (TDM) of these agents.</p><p><strong>Methods: </strong>Studies about costimulatory blockers in SOT in humans or animal transplant models in the past decade (2014-2024) were systematically reviewed in PubMed, European Union clinical trials (EudraCT), and ClinicalTrials.gov .</p><p><strong>Results: </strong>Seventy-five registered clinical trials and 58 published articles were found on costimulation blockade of the CD28-CD80/86, CD40-CD40L, and OX40-OX40L pathways. Belatacept, an antagonist of the CD28-CD80/86 pathway, is the only approved costimulatory agent in SOT, hence accounting for most of the research. Other identified costimulatory blocking agents included abatacept and CD28 antagonists tegoprubart, dazodalibep, and TNX-1500. Although tegoprubart was unsuccessful in pancreas transplantation in nonhuman primates, trials in human kidney transplantation are underway. Dazodalibep trials faced recruitment challenges. TNX-1500 was unsuccessful in animal studies and is currently not pursued in humans. After discontinuation of iscalimab (CD40-CD154 pathway antagonist) in SOT, the alternatives, bleselumab and KPL404, showed promising results in kidney transplantation and cardiac xenotransplantation. Studies on secondary costimulatory pathway antagonists, such as OX40-OX40L, have only used animal models. Despite the low interindividual variability in pharmacokinetics (PK) in all studied agents, TDM could be useful for optimizing dosing in PK/pharmacodynamic (PD) studies.</p><p><strong>Conclusions: </strong>The routine use of costimulation blockade in SOT is hindered by problems in efficacy compared with the standard of care. Costimulatory inhibitors could be combined in a calcineurin inhibitor-free regimen. Future PK/pharmacodynamic studies in costimulatory agents and personalized medicine could warrant TDM of these agents.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":"64-76"},"PeriodicalIF":2.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142682886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Examining Whole Blood, Total and Free Plasma Tacrolimus in Elderly Kidney Transplant Recipients.","authors":"Amelia R Cossart, Nicole M Isbel, Scott B Campbell, Brett McWhinney, Christine E Staatz","doi":"10.1097/FTD.0000000000001274","DOIUrl":"10.1097/FTD.0000000000001274","url":null,"abstract":"<p><strong>Background: </strong>Therapeutic monitoring is routinely performed to ensure tacrolimus whole-blood concentrations fall within a predefined target. Despite this, patients still experience inefficacy and toxicity that could be related to variability in free (unbound) tacrolimus exposure. Therefore, the aim of this study was to compare tacrolimus-free plasma (C u ), total plasma (C p ), and whole-blood (C wb ) concentrations in adult kidney transplant recipients and to characterize tacrolimus disposition across different matrices.</p><p><strong>Methods: </strong>Twelve-hour concentration-time profiling was performed in 15 recipients, allowing simultaneous measurement of C u , C p , and C wb . Pharmacokinetic parameters were estimated using noncompartmental analysis. The relationship between C wb and C p were examined using a capacity-limited binding model, incorporating the hematocrit fraction ( fHCT ) to estimate maximum binding concentration ( Bmax ) and dissociation constant ( Kd ). The relationship between C p and C u was evaluated using a linear binding model to estimate the nonspecific binding parameter ( Nplasma ). Nonlinear regression analysis was used to obtain estimates of Bmax , Kd , and Nplasma .</p><p><strong>Results: </strong>A total of 195 paired C wb , C p , and C u values were collected. The median ratios of C wb :C p , C p :C u , and C wb :C u were 9:1, 20:1, and 138:1, respectively. Variability in free plasma exposure was large; free trough values ranged from 8 to 51 ng/L and free area-under-the-concentration-time-curve values ranged from 424 to 7160 ng·h/L. Median (range) estimates of Bmax , Kd , and Nplasma were 90.4 µg/L (22.4-752.5 µg/L), 2.36 µg/L (0-69.2 µg/L), and 0.05 (0.035-0.085), respectively. The interindividual variability (CV%) in binding parameters was considerable ( Bmax 117.2%; Nplasma 32.5%).</p><p><strong>Conclusions: </strong>Large variability was observed in tacrolimus-free plasma exposure and binding parameters. Future research to characterize the relationship between tacrolimus C u and patient outcomes may be of benefit.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":"47 1","pages":"161-168"},"PeriodicalIF":2.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142962435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world Plasma Exposure of Nirmatrelvir/Ritonavir in Chinese Hospitalized Patients With COVID-19: A Multicenter Retrospective Study.","authors":"Zhiyuan Ma, Mengru Bai, Shuying Shen, Junshan Zhou, Rong Dong, Jiangjun Zhang, Yayun Weng, Li Li, Yongchen Li, Dan Liu, Wei Yan, Nengming Lin, Jianmei Xia","doi":"10.1097/FTD.0000000000001305","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001305","url":null,"abstract":"<p><strong>Background: </strong>Nirmatrelvir/ritonavir is licensed for the treatment of mild-to-moderate coronavirus disease (COVID-19) in patients at an increased risk of progression to severe disease. However, data on the real-world plasma exposure to nirmatrelvir/ritonavir remain limited, particularly in Chinese patients. This study aimed to assess the nirmatrelvir/ritonavir trough concentration (Ctrough) and identify its critical factors in hospitalized Chinese patients treated with nirmatrelvir/ritonavir 300 mg/100 mg twice daily over a 5-day course.</p><p><strong>Methods: </strong>A high-performance liquid chromatography-tandem mass spectrometry assay was developed and validated to measure the nirmatrelvir/ritonavir Ctrough. Correlation analyses were performed to identify the variables influencing nirmatrelvir/ritonavir Ctrough.</p><p><strong>Results: </strong>Among the 110 patients, 100% had plasma concentrations above the antiviral in vitro 90% effective concentration. The median Ctrough of nirmatrelvir was 4.55 mcg/mL (15.6× 90% effective concentration), ranging from 0.65 to 12.44 mcg/mL. Nirmatrelvir Ctrough in normal and mild renal impairment cohorts were comparable (4.09 ± 1.97 mcg/mL and 4.57 ± 2.21 mcg/mL) but significantly increased in the moderate renal impairment cohort (6.41 ± 2.31 mcg/mL). Sex, age, and obesity were not significantly associated with nirmatrelvir exposure.</p><p><strong>Conclusions: </strong>Nirmatrelvir Ctrough was high in Chinese patients with COVID-19, and therapeutic drug monitoring should not be routinely recommended, except in patients with renal impairment.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143068080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Analysis of 2 Commercially Available Assays for Therapeutic Drug Monitoring of Infliximab and Adalimumab.","authors":"Juan López Pérez, Mercedes Inda-Landaluce, Mercedes Nocito-Colón, Luis Martínez-Lostao","doi":"10.1097/FTD.0000000000001295","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001295","url":null,"abstract":"<p><strong>Background: </strong>Tumor necrosis factor is a crucial proinflammatory cytokine in immune-mediated diseases. Tumor necrosis factor inhibitors (TNFi), such as infliximab and adalimumab, effectively treat rheumatological and digestive disorders. However, challenges such as primary nonresponse, secondary treatment failure, or adverse reactions limit their efficacy. Monitoring TNFi levels is essential for optimizing treatment and improving outcomes. An enzyme-linked immunosorbent assay (ELISA; Promonitor) was compared with 2 commercially available methods for quantifying infliximab and adalimumab levels: the chemiluminescence assay (i-Track10) and fluorescence assay (Afias-10).</p><p><strong>Methods: </strong>Serum samples from 166 patients with inflammatory bowel disease were analyzed. Drug levels were measured using i-Track10, Afias-10, and Promonitor. Spearman's correlation analysis, Bland-Altman analysis, analysis of differences, Passing-Bablok regression, and Cohen kappa for agreement assessment were used for statistical analysis.</p><p><strong>Results: </strong>Strong correlations were observed between Promonitor and Afias-10 for infliximab (rs = 0.982) and adalimumab (rs = 0.972), and with i-Track10 (rs = 0.935 for infliximab, rs = 0.947 for adalimumab). However, significant differences indicated noninterchangeability with ELISA. Passing-Bablok regression showed systematic and proportional biases. Cohen kappa exhibited higher concordance with Afias-10 for therapeutic ranges (κ = 0.962 for infliximab, κ = 0.849 for adalimumab) compared with i-Track10.</p><p><strong>Conclusions: </strong>Afias-10 and i-Track10 are suitable for TNFi monitoring but are not interchangeable with ELISA. Consistent assay methods should be used for patient monitoring to ensure accuracy and reliability.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Approach for Improving the Detection and Quantitation of Buprenorphine and Its Metabolites in Maternal and Neonatal Hair.","authors":"Osama Y Alshogran, Wenchen Zhao, Elizabeth E Krans, Steve Caritis, Imam H Shaik, Raman Venkataramanan","doi":"10.1097/FTD.0000000000001291","DOIUrl":"10.1097/FTD.0000000000001291","url":null,"abstract":"<p><strong>Background: </strong>Buprenorphine (BUP) use is prevalent in pregnant women with opioid use disorder (OUD). Drug monitoring during pregnancy is critical for optimizing dosing regimen and achieving the desired clinical outcomes. Hair can be used as a critical biological matrix for monitoring long-term exposure to drugs. The aim of this study was to optimize the methodology used to quantify BUP and its metabolites in hair samples.</p><p><strong>Methods: </strong>Conditions for hair sample processing (ie, hair washing, incubation temperature, and extraction time) were optimized to maximize extraction recovery. The LC-MS/MS strategy employed here used 4 deuterated internal standards for quantifying BUP and its major metabolites [norbuprenorphine (NBUP), buprenorphine glucuronide (BUP-G), and norbuprenorphine-glucuronide (NBUP-G)] in human hair samples. The optimized conditions were used to measure BUP and its metabolites in hair samples of 5 women undergoing OUD treatment and their neonates.</p><p><strong>Results: </strong>Unwashed hair samples processed by shaking with acetonitrile for 24 hours at 37 °C showed higher BUP (36%) and NBUP (67%) recovery, compared with those processed by incubation at room temperature. The standard curves showed excellent linearity over 0.05-100 ng/mL for BUP and NBUP and 0.1-200 ng/mL for BUP-G and NBUP-G. The assay was partially validated for reproducibility and accuracy and was successfully used for measuring BUP and metabolites in aforementioned hair samples. BUP was identified in all hair samples, while BUP-G was not. BUP was the primary analyte in maternal hair (median: 38.3 pg/mg; 25-75 percentile: 17-152.4 pg/mg), while NBUP-G was predominant in neonatal hair (median: 28.6 pg/mg; 25%-75% percentile: 1.9-112.8 pg/mg).</p><p><strong>Conclusions: </strong>The methodology used for quantifying BUP and its metabolites in hair samples of maternal female patients and their neonates is simple, accurate, and reproducible. The developed method may be useful for measuring fetal exposure to BUP during gestation.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Personalized Dosing of Linezolid to Reduce the Risk of Thrombocytopenia: A Systematic Review and Meta-Analysis.","authors":"Kazutaka Oda, Takeru Tsuruta, Yuki Hanai, Tomoyuki Yamada, Toshiaki Komatsu, Shoji Kondo, Hirofumi Jono, Hideyuki Saito","doi":"10.1097/FTD.0000000000001300","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001300","url":null,"abstract":"<p><strong>Background: </strong>Linezolid-induced thrombocytopenia (LIT) occurs in a dose-dependent manner. There is no consensus regarding personalized dosing of linezolid in the real world. This study investigated the usefulness of personalized dosing for the potential mitigation of LIT compared with standard dosing.</p><p><strong>Methods: </strong>A systematic review and meta-analysis were performed using 4 medical electronic databases. Inclusion criteria were original research articles published up to October 23, 2023, whereas nonoriginal articles were excluded. Eligible participants included adults who were administered linezolid. A random-effects model was used to synthesize the results.</p><p><strong>Results: </strong>Four studies were eligible for inclusion. There were 208 patients in the personalized dosing (intervention) group and 195 patients in the standard dosing (comparison) group. The odds ratio for the intervention was 0.648 (95% confidence interval: 0.150-2.797), although significant heterogeneity was observed (I2 = 83.3%). An ad hoc analysis was performed by excluding one study with a significant bias risk in the treatment duration. The odds ratio for the intervention in the ad hoc analysis was 0.356 (95% confidence interval: 0.179-0.708) with little heterogeneity, showing a lower incidence risk of LIT.</p><p><strong>Conclusions: </strong>Personalized dosing in linezolid therapy may mitigate the risk of LIT.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiple Model Optimal Sampling Promotes Accurate Vancomycin Area-Under-the-Curve Estimation Using a Single Sample in Critically Ill Children.","authors":"Kevin J Downes, Anna Sharova, Judith Malone, Audrey R Odom John, Athena F Zuppa, Michael N Neely","doi":"10.1097/FTD.0000000000001293","DOIUrl":"10.1097/FTD.0000000000001293","url":null,"abstract":"<p><strong>Background: </strong>Area-under-the-curve (AUC)-directed vancomycin therapy is recommended; however, AUC estimation in critically ill children is difficult owing to the need for multiple samples and lack of informative models.</p><p><strong>Methods: </strong>The authors prospectively enrolled critically ill children receiving intravenous (IV) vancomycin for suspected infection and evaluated the accuracy of Bayesian estimation of AUC from a single, optimally timed sample. During the dosing interval, when clinical therapeutic drug monitoring was performed, an optimally timed sample was collected, which was determined for each subject using an established population pharmacokinetic model and the multiple model optimal function of Pmetrics, a nonparametric population pharmacokinetic modeling software. The model was embedded in InsightRx NOVA (InsightRx, Inc.) for individual Bayesian estimation of AUC using the optimal sample versus all available samples (optimally timed sample + clinical samples).</p><p><strong>Results: </strong>Eighteen children were included. The optimal sampling time to inform Bayesian estimation of vancomycin AUC was highly variable, with trough samples being optimally informative in 32% of children. Optimal samples were collected by clinical nurses within 15 minutes of the goal time in 14 of 18 participants (78%). Compared with all samples, Bayesian AUC estimation with optimal samples had a mean bias of 0.4% (±5.9%) and mean imprecision of 4.6% (±3.6%). Bias of optimal sampling was <10% for 17 of the 18 participants (94%). When estimating AUC using only a peak sample (≤2 hours after dose) or only a trough (≤30 minutes before next dose), bias was <10% for 78% and 86% of participants, respectively.</p><p><strong>Conclusions: </strong>Optimal sampling supports accurate Bayesian estimation of vancomycin AUC from a single plasma sample in critically ill children.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of Teicoplanin Trough Concentrations and Safety Following High-Dose Loading in a Pediatric Population.","authors":"Sayaka Okuzono, Takaaki Yamada, Yoshitomo Motomura, Hikaru Kanemasa, Masataka Ishimura, Yuhki Koga, Hiroyuki Torisu, Shunsuke Kanno, Ichiro Ieiri, Shouichi Ohga","doi":"10.1097/FTD.0000000000001302","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001302","url":null,"abstract":"<p><strong>Background: </strong>Therapeutic drug monitoring-informed teicoplanin dosage adjustments are recommended for safe and effective use. The authors' group previously reported that only half of children reached the recommended blood concentration range at the standard teicoplanin loading dose. It has been suggested that higher loading doses are necessary; however, the usefulness and safety of high-dose loading in pediatric patients in clinical practice are unknown.</p><p><strong>Methods: </strong>This retrospective cohort study was conducted between January 2018 and June 2021 using electronic medical records. The analysis included 2- to 16-year-old patients treated with teicoplanin who met the eligibility criteria. We assessed the trough concentration of teicoplanin and its safety after high-dose loading in pediatric patients.</p><p><strong>Results: </strong>Overall, 86 patients received a high-dose loading regimen (15 mg/kg every 12 hours for 3 doses, followed by 10 mg/kg once daily). Notably, 55 of the 86 patients (64%) achieved the target trough concentration (>15 mg/L) at significantly higher rates without increasing the incidence of organ damage compared with the standard loading regimen. Multivariate analysis revealed significant differences in age and renal function as factors that inhibited the attainment of the target trough concentration. Simulation analysis using a nomogram stratified by age and renal function revealed that the predicted teicoplanin trough levels were within the target trough values in 73% of patients.</p><p><strong>Conclusions: </strong>High-dose teicoplanin loading safely increases trough blood concentrations in the pediatric population. For further optimization, the dose selection should be stratified according to age and renal function.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142955500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}