Therapeutic Drug Monitoring最新文献

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Real-world Plasma Exposure of Nirmatrelvir/Ritonavir in Chinese Hospitalized Patients With COVID-19: A Multicenter Retrospective Study. 中国住院COVID-19患者尼马特瑞韦/利托那韦的真实血浆暴露:一项多中心回顾性研究
IF 2.8 4区 医学
Therapeutic Drug Monitoring Pub Date : 2025-01-30 DOI: 10.1097/FTD.0000000000001305
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
{"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}
引用次数: 0
Multiple Model Optimal Sampling Promotes Accurate Vancomycin Area-Under-the-Curve Estimation Using a Single Sample in Critically Ill Children. 多模型最优抽样促进危重儿童使用单一样本进行准确的万古霉素曲线下面积估计。
IF 2.8 4区 医学
Therapeutic Drug Monitoring Pub Date : 2025-01-23 DOI: 10.1097/FTD.0000000000001293
Kevin J Downes, Anna Sharova, Judith Malone, Audrey R Odom John, Athena F Zuppa, Michael N Neely
{"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}
引用次数: 0
Personalized Dosing of Linezolid to Reduce the Risk of Thrombocytopenia: A Systematic Review and Meta-Analysis. 利奈唑胺个体化剂量降低血小板减少风险:系统回顾和荟萃分析。
IF 2.8 4区 医学
Therapeutic Drug Monitoring Pub Date : 2025-01-23 DOI: 10.1097/FTD.0000000000001300
Kazutaka Oda, Takeru Tsuruta, Yuki Hanai, Tomoyuki Yamada, Toshiaki Komatsu, Shoji Kondo, Hirofumi Jono, Hideyuki Saito
{"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}
引用次数: 0
Investigation of Teicoplanin Trough Concentrations and Safety Following High-Dose Loading in a Pediatric Population. 替柯planin在儿童人群中高剂量负荷后谷浓度和安全性的研究。
IF 2.8 4区 医学
Therapeutic Drug Monitoring Pub Date : 2025-01-07 DOI: 10.1097/FTD.0000000000001302
Sayaka Okuzono, Takaaki Yamada, Yoshitomo Motomura, Hikaru Kanemasa, Masataka Ishimura, Yuhki Koga, Hiroyuki Torisu, Shunsuke Kanno, Ichiro Ieiri, Shouichi Ohga
{"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}
引用次数: 0
Determination of 31 Antimicrobials in Human Serum Using Ultra-High Performance Liquid Chromatography With Diode Array Detection for Application in Therapeutic Drug Monitoring. 超高效液相色谱-二极管阵列检测在治疗药物监测中的应用
IF 2.8 4区 医学
Therapeutic Drug Monitoring Pub Date : 2024-12-17 DOI: 10.1097/FTD.0000000000001284
Ibrahim El-Haffaf, Mehdi El Hassani, Amélie Marsot
{"title":"Determination of 31 Antimicrobials in Human Serum Using Ultra-High Performance Liquid Chromatography With Diode Array Detection for Application in Therapeutic Drug Monitoring.","authors":"Ibrahim El-Haffaf, Mehdi El Hassani, Amélie Marsot","doi":"10.1097/FTD.0000000000001284","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001284","url":null,"abstract":"<p><strong>Background: </strong>A versatile ultra-high performance liquid chromatography method with diode array detection was developed to quantify a wide range of antibiotics in human serum. This method addresses the need for rapid and accurate determination of antibiotic levels to ensure effective patient treatment and support the fight against antibiotic resistance.</p><p><strong>Methods: </strong>This method assesses 31 different compounds covering β-lactams, fluoroquinolones, antifungals, antituberculars, and more. Proteins were precipitated using methanol or acetonitrile, and drugs were extracted by liquid-liquid extraction with dichloromethane. Separation of the antimicrobials was achieved on a pentafluorophenyl column, using a mobile phase of phosphoric acid (0.01 mol/L) and acetonitrile in a gradient elution mode, with a flow rate of 500 μL/min.</p><p><strong>Results: </strong>Almost all compounds were detected at 200 nm. The total analysis time for this method was kept under 18 minutes, including equilibration time.</p><p><strong>Conclusions: </strong>This efficient method enables fast determination of numerous antimicrobial classes, providing clinicians with an essential tool for ensuring effective patient treatment and combating antimicrobial resistance.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847651","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}
引用次数: 0
Preliminary Determination of the Therapeutic Reference Range of Lurasidone in Chinese Patients and Analysis of the Factors Influencing Lurasidone Dose-Corrected Concentrations. 中国患者鲁拉西酮治疗参考范围的初步确定及影响鲁拉西酮剂量校正浓度的因素分析。
IF 2.8 4区 医学
Therapeutic Drug Monitoring Pub Date : 2024-12-12 DOI: 10.1097/FTD.0000000000001298
Ye Yang, Zhanzhang Wang, Tao Xiao, Xiaojia Ni, Emei Song, Lijing Dai, Yuqing Chen, Haoyang Lu, Dewei Shang, Yuguan Wen
{"title":"Preliminary Determination of the Therapeutic Reference Range of Lurasidone in Chinese Patients and Analysis of the Factors Influencing Lurasidone Dose-Corrected Concentrations.","authors":"Ye Yang, Zhanzhang Wang, Tao Xiao, Xiaojia Ni, Emei Song, Lijing Dai, Yuqing Chen, Haoyang Lu, Dewei Shang, Yuguan Wen","doi":"10.1097/FTD.0000000000001298","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001298","url":null,"abstract":"<p><strong>Background: </strong>The aim of this study was to determine the therapeutic reference range of lurasidone, and to analyze the factors influencing the dose-corrected concentration of lurasidone in Chinese psychiatric patients, thereby providing a basis for the development of individualized dosing of lurasidone.</p><p><strong>Methods: </strong>A retrospective analysis was conducted for hospitalized patients who had received lurasidone and undergone blood concentration monitoring from May 2022 to September 2023 at the Affiliated Brain Hospital of Guangzhou Medical University. Analyses were based on patient demographic data, treatment regimens, and administered drug concentrations.</p><p><strong>Results: </strong>Data for a total of 123 lurasidone steady-state trough concentrations were collected from 120 hospitalized patients. It was found that 85.56% of lurasidone steady-state trough concentrations were below the lower limit of the lurasidone therapeutic reference range (15 ng·mL-1), and that the median steady-state trough concentration was 7.09 ng·mL-1 (IQ1-IQ3 = 4.12-11.82 ng·mL-1). Gender, age, and co-medication with valproic acid were found to be significant factors influencing lurasidone steady-state trough concentration/daily dose (C/D) values. C/D values for females were 14% higher than those obtained for males. Among patients who did not receive concomitant administration of valproic acid, the C/D values were 55% higher than those who had received co-administered valproic acid. Furthermore, C/D values obtained for elderly patients (≥60 years) were 140% higher than those recorded for adolescents (<18 years) and 157% higher than those in younger adults (18-60 years).</p><p><strong>Conclusions: </strong>The findings of this study indicated that the guideline-recommended therapeutic reference range (15-40 ng·mL-1) for lurasidone may not be appropriate, at least for the Chinese population. More extensive therapeutic drug monitoring is recommended for elderly female patients and those receiving co-medication with lurasidone and valproic acid.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819265","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}
引用次数: 0
Clinical Efficacy and Safety of Vancomycin Based on Unbound Vancomycin Concentration Monitoring. 基于非结合万古霉素浓度监测的万古霉素临床疗效及安全性。
IF 2.8 4区 医学
Therapeutic Drug Monitoring Pub Date : 2024-12-10 DOI: 10.1097/FTD.0000000000001292
Fefei Ren, Shan Li, Yixin Liu, Xiangchen Li, Xikun Wu, Zhiqing Zhang
{"title":"Clinical Efficacy and Safety of Vancomycin Based on Unbound Vancomycin Concentration Monitoring.","authors":"Fefei Ren, Shan Li, Yixin Liu, Xiangchen Li, Xikun Wu, Zhiqing Zhang","doi":"10.1097/FTD.0000000000001292","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001292","url":null,"abstract":"<p><strong>Objective: </strong>To monitor total trough concentration (Cmin_total) and unbound trough concentration (Cmin_free) of vancomycin in clinical samples and analyze the factors influencing them, and to assess their correlation with clinical efficacy and acute kidney injury (AKI).</p><p><strong>Methods: </strong>Plasma samples were processed by protein precipitation, followed by hollow-fiber centrifugal ultrafiltration to separate unbound vancomycin from plasma. Thereafter, Cmin_total and Cmin_free were determined using high-performance liquid chromatography. Clinical data of patients were collected. Factors affecting vancomycin Cmin_total, Cmin_free, and their correlation with clinical efficacy and nephrotoxicity were investigated.</p><p><strong>Results: </strong>A total of 146 samples from 105 included patients were collected. Cmin_total and Cmin_free of vancomycin ranged from 0.62 to 56.08 mcg·mL-1 and 0.61-38.51 mcg·mL-1, respectively. Cmin_total and Cmin_free were correlated (r = 0.8899), influenced by basal creatinine and cystatin C. Higher level of Cmin_free (˃8.6 mcg·mL-1) and nephrotoxic drugs concomitant were risk factors of vancomycin-associated AKI (P < 0.05); Cmin_total and Cmin_free thresholds of vancomycin-associated AKI were 15.35 and 6.83 mcg·mL-1, respectively.</p><p><strong>Conclusions: </strong>vancomycin Cmin_total and Cmin_free, higher Cmin_total and Cmin_free were correlated and higher concentrations of both may increase the risk of AKI.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142808279","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}
引用次数: 0
Dose Optimization of Amikacin in the Emergency Department: A Population Pharmacokinetics Simulation Study. 急诊阿米卡星剂量优化:人群药代动力学模拟研究。
IF 2.8 4区 医学
Therapeutic Drug Monitoring Pub Date : 2024-12-03 DOI: 10.1097/FTD.0000000000001279
Nada Dia, Sabrina De Winter, Matthias Gijsen, Stefanie Desmet, Peter Vanbrabant, Willy Peetermans, Isabel Spriet, Erwin Dreesen
{"title":"Dose Optimization of Amikacin in the Emergency Department: A Population Pharmacokinetics Simulation Study.","authors":"Nada Dia, Sabrina De Winter, Matthias Gijsen, Stefanie Desmet, Peter Vanbrabant, Willy Peetermans, Isabel Spriet, Erwin Dreesen","doi":"10.1097/FTD.0000000000001279","DOIUrl":"10.1097/FTD.0000000000001279","url":null,"abstract":"<p><strong>Background: </strong>In adult patients with sepsis or septic shock admitted to the emergency department, a single intravenous 15 mg/kg amikacin dose provides inadequate pharmacokinetic-pharmacodynamic target attainment at the locally reported minimum inhibitory concentration (MIC) of 2 mg/L and the European Committee on Antimicrobial Susceptibility Testing clinical breakpoint for Enterobacterales of 8 mg/L.</p><p><strong>Objectives: </strong>To provide an amikacin dosing strategy with a clinically acceptable probability of target attainment (PTA) for all patients.</p><p><strong>Methods: </strong>Stochastic simulations were performed using a two-compartment population pharmacokinetics model of amikacin (NONMEM 7.5). PTA was evaluated for various dosing strategies across a range of virtual patients' body weight, body mass index, serum total protein, serum sodium, fluid balance, and estimated glomerular filtration rate according to the Chronic Kidney Disease Epidemiology Collaboration equation (eGFRCKD-EPI), at the locally reported MIC of 2 mg/L and the clinical breakpoint of 8 mg/L. The pharmacokinetic-pharmacodynamic targets were a 24-hour area under the concentration-time curve (AUC24h)/MIC of ≥80 and a 24-hour postdose concentration (C24h) of < 3 mg/L for efficacy and safety, respectively.</p><p><strong>Results: </strong>The PTA for the clinical breakpoint of 8 mg/L was <90% with standard 15 mg/kg dosing, across all patient characteristics. A flat 1500-mg dose achieved ≥90% PTA for the entire population at a MIC of 2 mg/L. However, at the clinical breakpoint of 8 mg/L, a flat 3500-mg dose provided ≥90% PTA only when the eGFRCKD-EPI was <96 mL/min/1.73 m2. The C24h was similar for 1500 mg and 15 mg/kg dosing, whereas 3500 mg resulted in a higher C24h.</p><p><strong>Conclusions: </strong>A flat dose is recommended over weight-based dosing. However, selecting a 1500-mg or 3500-mg dose may compromise either efficacy (MIC 2 mg/L) or safety (clinical breakpoint 8 mg/L), posing a dilemma. Clinical validation is warranted.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142772639","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}
引用次数: 0
Examining Whole Blood, Total and Free Plasma Tacrolimus in Elderly Kidney Transplant Recipients. 研究老年肾移植受者的全血、总血浆和游离血浆中的他克莫司。
IF 2.8 4区 医学
Therapeutic Drug Monitoring Pub Date : 2024-11-07 DOI: 10.1097/FTD.0000000000001274
Amelia R Cossart, Nicole M Isbel, Scott B Campbell, Brett McWhinney, Christine E Staatz
{"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 (Cu), total plasma (Cp), and whole-blood (Cwb) 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 Cu, Cp, and Cwb. Pharmacokinetic parameters were estimated using noncompartmental analysis. The relationship between Cwb and Cp 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 Cp and Cu 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 Cwb, Cp, and Cu values were collected. The median ratios of Cwb:Cp, Cp:Cu, and Cwb:Cu 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 Cu and patient outcomes may be of benefit.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605619","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}
引用次数: 0
Maternal Serum and Cord Blood Levels of Levetiracetam and Valproate at Delivery and Their Associations With Neonatal Abstinence-Related Symptoms. 分娩时产妇血清和脐带血中的左乙拉西坦和丙戊酸钠水平及其与新生儿戒断相关症状的关系。
IF 2.8 4区 医学
Therapeutic Drug Monitoring Pub Date : 2024-10-15 DOI: 10.1097/FTD.0000000000001271
Shusuke Ozawa, Natsuko Matsuzawa, Chiho Fuseya, Norihiko Kikuchi, Tanri Shiozawa, Takafumi Naito
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