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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 Q2 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2024-12-17 DOI: 10.1097/FTD.0000000000001284
Ibrahim El-Haffaf, Mehdi El Hassani, Amélie Marsot

Background: 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.

Methods: 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.

Results: Almost all compounds were detected at 200 nm. The total analysis time for this method was kept under 18 minutes, including equilibration time.

Conclusions: 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.

背景:建立了一种多功能的二极管阵列检测的超高效液相色谱法,用于定量测定人血清中的多种抗生素。该方法解决了快速准确测定抗生素水平的需求,以确保有效的患者治疗并支持对抗抗生素耐药性。方法:该方法评估了31种不同的化合物,包括β-内酰胺类、氟喹诺酮类、抗真菌药、抗结核药等。蛋白质用甲醇或乙腈沉淀,药物用二氯甲烷液液萃取。采用五氟苯基色谱柱,流动相为磷酸(0.01 mol/L)和乙腈,梯度洗脱,流速为500 μL/min。结果:几乎所有化合物均在200 nm处检出。该方法的总分析时间保持在18分钟以下,包括平衡时间。结论:这种有效的方法能够快速测定多种抗菌素类别,为临床医生提供了确保有效治疗患者和对抗抗菌素耐药性的重要工具。
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引用次数: 0
Misleading Renal Function Evaluation Leading to Severe Methotrexate-Induced Toxicity. 误导肾功能评估导致严重的甲氨蝶呤诱导毒性。
IF 2.8 4区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2024-12-17 DOI: 10.1097/FTD.0000000000001297
Manon Launay, Manon Vogrig, Marlene Damin-Pernik, Hubert Marotte, Sophie Perinel-Ragey

Abstract: Low-dose methotrexate has been proposed as therapy for patients with severely disabling psoriasis and psoriatic arthritis. However, it can be associated with severe toxicity, such as pancytopenia, characterized by anemia (hemoglobin level <13 g/dL in men), thrombocytopenia (platelet count <150 × 109/L), and neutropenia or agranulocytosis (neutrophil count <1.5 × 109/L and 0.5 × 109/L, respectively). Here, we report a challenging clinical scenario characterized by pancytopenia and acute renal failure to inform clinicians about potential drug-drug interactions and subclinical renal insufficiency.

摘要:低剂量甲氨蝶呤已被提议作为严重致残性银屑病和银屑病关节炎患者的治疗方法。然而,它可能会产生严重的毒性,如泛发性贫血,其特征是贫血(血红蛋白水平低于正常值)。
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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 Q2 MEDICAL LABORATORY TECHNOLOGY 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

Background: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

背景:本研究旨在确定鲁拉西酮的治疗参考范围,分析影响我国精神病患者鲁拉西酮剂量校正浓度的因素,为鲁拉西酮个体化给药提供依据。方法:回顾性分析广州医科大学附属脑科医院2022年5月至2023年9月期间接受鲁拉西酮治疗并进行血药浓度监测的住院患者。分析基于患者人口统计数据、治疗方案和给药浓度。结果:从120例住院患者中收集了123个鲁拉西酮稳态谷浓度数据。85.56%的鲁拉西酮稳态谷浓度低于鲁拉西酮治疗参考范围下限(15 ng·mL-1),中位稳态谷浓度为7.09 ng·mL-1 (IQ1-IQ3 = 4.12-11.82 ng·mL-1)。性别、年龄和与丙戊酸的联合用药是影响鲁拉西酮稳态谷浓度/日剂量(C/D)值的重要因素。女性的C/D值比男性高14%。在未同时服用丙戊酸的患者中,C/D值比同时服用丙戊酸的患者高55%。此外,老年患者(≥60岁)的C/D值比青少年患者高140%(结论:本研究结果表明,指南推荐的鲁拉西酮治疗参考范围(15-40 ng·mL-1)可能不合适,至少对中国人群不合适。建议对老年女性患者和与鲁拉西酮和丙戊酸联合用药的患者进行更广泛的治疗药物监测。
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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 Q2 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2024-12-10 DOI: 10.1097/FTD.0000000000001292
Fefei Ren, Shan Li, Yixin Liu, Xiangchen Li, Xikun Wu, Zhiqing Zhang

Objective: 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).

Methods: 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.

Results: 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.

Conclusions: 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.

目的:监测万古霉素临床样品的总谷浓度(Cmin_total)和游离谷浓度(Cmin_free),分析其影响因素,并评价其与临床疗效和急性肾损伤(AKI)的相关性。方法:血浆样品经蛋白沉淀处理后,采用中空纤维离心超滤分离血浆中未结合的万古霉素。然后用高效液相色谱法测定Cmin_total和Cmin_free。收集患者的临床资料。探讨万古霉素Cmin_total、Cmin_free的影响因素及其与临床疗效和肾毒性的相关性。结果:共收集105例患者标本146份。万古霉素的Cmin_total和Cmin_free分别为0.62 ~ 56.08 mcg·mL-1和0.61 ~ 38.51 mcg·mL-1。Cmin_total和Cmin_free呈相关性(r = 0.8899),受基础肌酐和胱抑素c的影响。Cmin_free水平升高(8.6 mcg·mL-1)和肾毒性药物的伴随是万古霉素相关性AKI的危险因素(P < 0.05);万古霉素相关AKI的Cmin_total和Cmin_free阈值分别为15.35和6.83 mcg·mL-1。结论:万古霉素Cmin_total和Cmin_free与较高的Cmin_total和Cmin_free存在相关性,两者浓度较高均可增加AKI的发生风险。
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引用次数: 0
Unbound Ceftriaxone Concentrations in Plasma Measured Using Ultrafiltration Versus Equilibrium Dialysis: A Short Communication. 使用超滤与平衡透析测量血浆中非结合头孢曲松浓度:短通信。
IF 2.8 4区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2024-12-10 DOI: 10.1097/FTD.0000000000001294
Matthias Gijsen, Dorian Vanneste, Pieter Annaert, Yves Debaveye, Joost Wauters, Isabel Spriet

Background: Ceftriaxone is a first-line beta-lactam antibiotic used in diverse clinical settings. Owing to pharmacokinetic alterations, ceftriaxone therapeutic drug monitoring is currently recommended for patients in the intensive care unit. Ultrafiltration is typically used to measure unbound ceftriaxone concentrations, as it is less costly and time-consuming compared with equilibrium dialysis. However, the reference method, equilibrium dialysis, has not been compared with equilibrium dialysis for ceftriaxone to measure the unbound ceftriaxone concentrations. Therefore, unbound ceftriaxone fractions measured by ultrafiltration versus equilibrium dialysis were compared in patients in the intensive care unit.

Methods: Total and unbound ceftriaxone plasma fractions were measured by ultrafiltration (9500g at 37°C for 30 minutes) and equilibrium dialysis (12 kDa, 37°C for 4 hours) in 32 plasma samples from 28 patients who were critically ill collected during a previous prospective pharmacokinetic study. Passing-Bablok regression and Bland-Altman analyses were performed to evaluate the agreements between both methods.

Results: The median (range) total ceftriaxone plasma concentration was 108.6 (5.2-233) mg/L. The median unbound concentration measured by equilibrium dialysis and ultrafiltration was 14.5 (0.7-52.9) and 23.3 (0.9-79.2) mg/L, respectively, showing a significant difference. Passing-Bablok regression analysis revealed significant proportional and systematic bias. This result was confirmed by Bland-Altman analysis, with a mean relative bias of 43.3% and wide agreement limits (-21% to 108%).

Conclusions: Ultrafiltration substantially overestimates the unbound ceftriaxone fraction compared with equilibrium dialysis at 37°C. It is important to report methodological details and consider this information when interpreting unbound fractions of ceftriaxone and other drugs. These findings may impact the therapeutic drug monitoring of ceftriaxone.

背景:头孢曲松是一线β -内酰胺类抗生素,用于多种临床环境。由于药代动力学的改变,头孢曲松治疗药物监测目前被推荐用于重症监护病房的患者。超滤通常用于测量非结合头孢曲松浓度,因为与平衡透析相比,它成本更低,耗时更短。然而,尚未将参考方法平衡透析与头孢曲松平衡透析进行比较,以测量头孢曲松未结合浓度。因此,在重症监护病房的患者中,超滤和平衡透析测量的非结合头孢曲松馏分进行了比较。方法:采用超滤法(9500g, 37°C, 30分钟)和平衡透析法(12 kDa, 37°C, 4小时)对28例危重患者的32份血浆样本进行头孢曲松总血浆和非结合血浆组分的测定。采用passingbablok回归和Bland-Altman分析来评价两种方法之间的一致性。结果:头孢曲松总血药浓度中位(范围)为108.6 (5.2 ~ 233)mg/L。平衡透析和超滤测得的中位非结合浓度分别为14.5(0.7-52.9)和23.3 (0.9-79.2)mg/L,差异有统计学意义。Passing-Bablok回归分析显示显著的比例偏差和系统偏差。Bland-Altman分析证实了这一结果,平均相对偏差为43.3%,一致性范围很广(-21%至108%)。结论:与37°C的平衡透析相比,超滤大大高估了未结合的头孢曲松组分。在解释头孢曲松和其他药物的未结合部分时,报告方法学细节和考虑这些信息是很重要的。这些发现可能会影响头孢曲松的治疗药物监测。
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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 Q2 MEDICAL LABORATORY TECHNOLOGY 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

Background: 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.

Objectives: To provide an amikacin dosing strategy with a clinically acceptable probability of target attainment (PTA) for all patients.

Methods: 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.

Results: 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.

Conclusions: 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.

背景:在急诊住院的成年脓毒症或感染性休克患者中,单次静脉注射15mg /kg阿米卡星剂量不足以达到当地报告的最低抑制浓度(MIC) 2mg /L和欧洲抗微生物药敏试验委员会肠杆菌临床断点8mg /L的药代动力学-药效学目标。目的:为所有患者提供具有临床可接受的目标实现概率(PTA)的阿米卡星给药策略。方法:采用双室群体药代动力学模型(NONMEM 7.5)进行随机模拟。根据慢性肾脏病流行病学协作方程(eGFRCKD-EPI),在当地报道的MIC为2mg /L和临床断点为8mg /L时,评估了PTA在虚拟患者体重、体重指数、血清总蛋白、血清钠、体液平衡和肾小球滤过率的各种给药策略。药动药效学指标分别为浓度-时间曲线下24小时面积(AUC24h)/MIC≥80和给药后24小时浓度(C24h) < 3mg /L。结果:8mg /L的临床突破点PTA为:结论:相对于体重给药,建议采用平给药。然而,选择1500 mg或3500 mg的剂量可能会损害疗效(MIC为2 mg/L)或安全性(临床断点为8 mg/L),造成两难境地。临床验证是必要的。
{"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":"https://doi.org/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
Therapeutic Drug Monitoring of Nirmatrelvir/Ritonavir (Paxlovid) in Patients Treated for COVID-19: Results from a Prospective Multicenter Observational Study. 一项前瞻性多中心观察性研究的结果:尼马特利韦/利托那韦(Paxlovid)治疗COVID-19患者的药物监测
IF 2.8 4区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2024-12-03 DOI: 10.1097/FTD.0000000000001290
Corinna R Böger, Jens Martens-Lobenhoffer, Hans Worthmann, Dirk O Stichtenoth, Torben Brod

Background: Paxlovid is a combination of the antiviral agents nirmatrelvir and ritonavir indicated for the oral treatment of high-risk, symptomatic patients with coronavirus disease 2019 (COVID-19). As real-world data on the plasma concentrations of nirmatrelvir/ritonavir (Paxlovid) are limited, the aim of this study was to investigate nirmatrelvir/ritonavir plasma trough levels in a clinical setting using therapeutic drug monitoring.

Methods: A prospective, noninterventional, multicenter, observational clinical study was conducted in which the plasma trough levels of nirmatrelvir/ritonavir were simultaneously determined by using liquid chromatography tandem mass spectrometry in patients with symptomatic COVID-19. The blood samples were collected on days 1, 3, and 5 after the first full-dose day (day 0), and patient data such as sex, height, weight, renal function, liver enzymes, and concomitant (co-) medications were obtained to describe the plasma levels with respect to potential influencing factors.

Results: A total of 46 blood samples from 21 patients were analyzed. The geometric mean Cmin was 4997 ng/mL for nirmatrelvir and 529.4 ng/mL for ritonavir. The plasma concentrations covered a wide range, the highest being observed in patients with advanced age and renally excreted comedications. Patients older than 65 years had a significantly higher risk of achieving excessive plasma trough concentrations above 8840 ng/mL for nirmatrelvir and 1440 ng/mL for ritonavir compared with younger patients (odds ratio 11.2, 95% confidence interval 1.04-120.4).

Conclusions: The plasma trough concentrations of nirmatrelvir and ritonavir in patients treated for symptomatic COVID-19 were higher than the reference values of 2210 ng/mL for nirmatrelvir and 360 ng/mL for ritonavir stated in the product characteristics. Advanced age and renally eliminated comedication were identified as possible influencing factors that warrant further investigation.

背景:Paxlovid是抗病毒药物尼马特里韦和利托那韦的联合用药,适用于口服治疗高危症状性冠状病毒病2019 (COVID-19)患者。由于现实世界中关于尼马特利韦/利托那韦(Paxlovid)血浆浓度的数据有限,本研究的目的是通过治疗药物监测在临床环境中研究尼马特利韦/利托那韦的血浆低谷水平。方法:采用前瞻性、非介入性、多中心、观察性临床研究,采用液相色谱-串联质谱法同时检测有症状的COVID-19患者血浆中尼马特利韦/利托那韦的谷水平。在第一个全剂量日(第0天)后的第1、3和5天采集血样,获得患者的性别、身高、体重、肾功能、肝酶和伴随(联合)药物等数据,以描述血浆水平及其潜在影响因素。结果:共分析了21例患者46份血样。尼马特瑞韦和利托那韦的几何平均Cmin分别为4997 ng/mL和529.4 ng/mL。血浆浓度覆盖范围很广,在高龄和肾脏排泄药物的患者中观察到的浓度最高。年龄大于65岁的患者与年轻患者相比,尼马特利韦和利托那韦的血浆谷浓度分别高于8840 ng/mL和1440 ng/mL的风险明显更高(优势比11.2,95%可信区间1.04-120.4)。结论:症状性COVID-19治疗患者的尼马特利韦和利托那韦血药谷浓度均高于产品特性中尼马特利韦2210 ng/mL和利托那韦360 ng/mL的参考值。高龄和肾脏停用药物被确定为可能的影响因素,值得进一步调查。
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引用次数: 0
One Concentration Does Not Fit All: It is Time to Personalize the Therapeutic Range of Infliximab in Crohn Disease. 一个浓度不适合所有:是时候个性化英夫利昔单抗治疗克罗恩病的范围。
IF 2.8 4区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2024-11-27 DOI: 10.1097/FTD.0000000000001251
Bénédicte Franck, Camille Tron, Marie-Clémence Verdier, Eric Bellissant, Anne-Sophie Peaucelle, Xavier Roblin, Florian Lemaitre, Guillaume Bouguen

Background: Therapeutic drug monitoring of infliximab is commonly performed based on trough concentration. However, doses and dosing intervals may be adapted to patient outcomes, and this trough concentration target may correspond to a large range of exposures in terms of the area under the concentration-time curve (AUC). The objectives of this study were to assess the real-life exposure to intravenous infliximab in patients with Crohn disease in remission at year 1 and to assess the evolution of exposure in patients who switched to subcutaneous infliximab.

Methods: The authors conducted a retrospective observational pharmacokinetic study in patients with Crohn disease who had available infliximab concentrations during intravenous and subcutaneous infliximab maintenance therapy as per the standard of care. Infliximab exposure parameters (AUCs and trough concentrations, C0) were compared for different dosing regimens of intravenous infliximab before (intravenous) and after (subcutaneous) the switch.

Results: A total of 113 patients had 383 intravenous infliximab concentrations. Dosing intervals ranged from 4 to 12 weeks. The median/range/CV% C0, AUC0-t, and AUC0-8weeks were 5.3 mcg/mL [

Conclusions: In this study, the authors suggested that in patients treated with IV IFX, different targets of C0 should be proposed according to treatment schemes and that AUC0-t might be a relevant determinant of clinical remission. Moreover, exposure did not remain stable throughout the switch from IV to SC IFX in any patient. These variations may depend on the intravenous dosing interval before switching.

背景:英夫利昔单抗的治疗药物监测通常基于谷浓度。然而,剂量和给药间隔可以根据患者的结果进行调整,并且就浓度-时间曲线(AUC)下的面积而言,这个谷浓度目标可能对应于大范围的暴露。本研究的目的是评估克罗恩病1年缓解期患者静脉注射英夫利昔单抗的真实暴露情况,并评估转而皮下注射英夫利昔单抗的患者暴露情况的演变。方法:作者对克罗恩病患者进行了回顾性观察性药代动力学研究,这些患者在静脉注射和皮下注射英夫利昔单抗维持治疗期间可获得英夫利昔单抗浓度,按照护理标准。比较了英夫利昔单抗在静脉注射前(静脉注射)和注射后(皮下注射)不同给药方案的暴露参数(auc和谷浓度,C0)。结果:113例患者静脉注射英夫利昔单抗383次。给药间隔为4至12周。中位/范围/CV% C0、AUC0-t和auc0 -8周均为5.3 mcg/mL[结论:在本研究中,作者建议在IV IFX治疗的患者中,应根据治疗方案提出不同的C0靶点,AUC0-t可能是临床缓解的相关决定因素。]此外,在从IV到SC IFX的转换过程中,任何患者的暴露都没有保持稳定。这些变化可能取决于切换前的静脉给药间隔。
{"title":"One Concentration Does Not Fit All: It is Time to Personalize the Therapeutic Range of Infliximab in Crohn Disease.","authors":"Bénédicte Franck, Camille Tron, Marie-Clémence Verdier, Eric Bellissant, Anne-Sophie Peaucelle, Xavier Roblin, Florian Lemaitre, Guillaume Bouguen","doi":"10.1097/FTD.0000000000001251","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001251","url":null,"abstract":"<p><strong>Background: </strong>Therapeutic drug monitoring of infliximab is commonly performed based on trough concentration. However, doses and dosing intervals may be adapted to patient outcomes, and this trough concentration target may correspond to a large range of exposures in terms of the area under the concentration-time curve (AUC). The objectives of this study were to assess the real-life exposure to intravenous infliximab in patients with Crohn disease in remission at year 1 and to assess the evolution of exposure in patients who switched to subcutaneous infliximab.</p><p><strong>Methods: </strong>The authors conducted a retrospective observational pharmacokinetic study in patients with Crohn disease who had available infliximab concentrations during intravenous and subcutaneous infliximab maintenance therapy as per the standard of care. Infliximab exposure parameters (AUCs and trough concentrations, C0) were compared for different dosing regimens of intravenous infliximab before (intravenous) and after (subcutaneous) the switch.</p><p><strong>Results: </strong>A total of 113 patients had 383 intravenous infliximab concentrations. Dosing intervals ranged from 4 to 12 weeks. The median/range/CV% C0, AUC0-t, and AUC0-8weeks were 5.3 mcg/mL [<LLoQ-49.6]/71.6%, 37,792 mcg.h/mL [4971-116,366]/33.1%, and 41,582 mcg.h/mL [7953-232,048]/43.9%, respectively. Forty-one patients had available paired C0 after both intravenous and subcutaneous administration. A poor correlation was found between preswitch intravenous infliximab C0 and postswitch subcutaneous infliximab C0.</p><p><strong>Conclusions: </strong>In this study, the authors suggested that in patients treated with IV IFX, different targets of C0 should be proposed according to treatment schemes and that AUC0-t might be a relevant determinant of clinical remission. Moreover, exposure did not remain stable throughout the switch from IV to SC IFX in any patient. These variations may depend on the intravenous dosing interval before switching.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142772640","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
Serum Concentration of Antidepressant Drugs in Geriatric Day Care Patients With Renal Insufficiency and Multimorbidity. 患有肾功能不全和多病的老年日间护理患者的抗抑郁药物血清浓度。
IF 2.8 4区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2024-11-26 DOI: 10.1097/FTD.0000000000001285
Sibylle Reber, Alexandra S Herr, Stefan Unterecker, Maike Scherf-Clavel

Background: Geriatric depression is challenging to treat owing to age-related changes in pharmacokinetics and comorbidities. Although renal insufficiency and multimorbidity are typical geriatric complications that cannot be completely separated from each other, no study has examined the influence of these factors on the serum concentrations of antidepressants. For the first time, we evaluated the effects of these factors in combination on the dose-corrected serum concentration (C/D) of antidepressants in geriatric patients.

Methods: In this retrospective study, data from 123 geriatric patients in a gerontopsychiatric day care unit at the University Hospital of Würzburg were analyzed. Multiple linear regression analysis and analysis of variance with confounders were used to examine the associations between glomerular filtration rate (GFR) and stages of renal impairment and the C/D of venlafaxine, mirtazapine, sertraline, and escitalopram corrected for multimorbidity, sex, lithium intake, and the number of triple whammy drugs.

Results: GFR (P < 0.001, ß = -0.070) was associated with the C/D of the active moiety of venlafaxine (N = 32). GFR, multimorbidity, and sex were not associated with the C/D of mirtazapine, escitalopram, or sertraline.

Conclusions: As the influence of sex may be less pronounced than that of decreasing GFR in terms of the C/D of the active moiety of venlafaxine in geriatric patients, we recommend considering the GFR for dose adjustment rather than sex. In conclusion, even in patients with mild renal impairment, serum venlafaxine concentration should be monitored to prevent overdosing. Mirtazapine, sertraline, and escitalopram may be well-suited antidepressants for geriatric patients with renal function impairment stage 2-3 as well as multimorbidity.

背景:由于老年药代动力学和并发症的变化,老年抑郁症的治疗具有挑战性。虽然肾功能不全和多病症是典型的老年并发症,两者不能完全分开,但还没有研究探讨过这些因素对抗抑郁药血清浓度的影响。我们首次评估了这些因素共同对老年患者抗抑郁药剂量校正血清浓度(C/D)的影响:在这项回顾性研究中,我们分析了维尔茨堡大学医院老年精神科日间护理病房 123 名老年患者的数据。采用多元线性回归分析和带混杂因素的方差分析来研究肾小球滤过率(GFR)和肾功能损害程度与文拉法辛、米氮平、舍曲林和艾司西酞普兰的C/D之间的关系,并对多病症、性别、锂摄入量和三联药物的数量进行了校正:肾小球滤过率(P < 0.001,ß = -0.070)与文拉法辛活性分子的C/D有关(N = 32)。GFR、多病症和性别与米氮平、艾司西酞普兰或舍曲林的C/D无关:由于在老年患者中,性别对文拉法辛活性分子C/D的影响可能不如肾小球滤过率下降那么明显,因此我们建议在调整剂量时考虑肾小球滤过率而不是性别。总之,即使是肾功能轻度受损的患者,也应监测血清文拉法辛的浓度,以防用药过量。米氮平、舍曲林和艾司西酞普兰可能是非常适合肾功能受损2-3期以及多病的老年患者的抗抑郁药物。
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引用次数: 0
Midazolam Boosting With Cobicistat in a Patient With Drug-Resistant Epilepsy and Focal Status Epilepticus. 在一名耐药性癫痫和局灶性癫痫患者中使用咪达唑仑与考比司他联合治疗。
IF 2.8 4区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2024-11-20 DOI: 10.1097/FTD.0000000000001283
Tessa Born-Bondt van den, Niels Westra, Katarzyna Krzywicka, Harmen R Moes, Manon Schuls-Fouchier, Daan J Touw, Oude Munnink Thijs H

Background: This report presents the case of a patient with drug-resistant epilepsy. Despite treatment with 4 antiepileptic drugs, the patient experienced an increasing frequency of focal seizures, necessitating hospitalization, and continuous intravenous midazolam infusion.

Methods: Cobicistat was introduced as a pharmacokinetic booster to decrease the metabolic clearance of midazolam, leading to increased exposure and an extended half-life.

Results: Cobicistat boosting allowed the switch from intravenous to oral midazolam, and the patient was discharged on an oral midazolam regimen.

Conclusions: Cobicistat can be effectively used to boost midazolam exposure pharmacokinetically in patients with drug-resistant epilepsy who require stable midazolam blood concentrations.

背景:本报告介绍了一名耐药性癫痫患者的病例。尽管接受了 4 种抗癫痫药物的治疗,但患者的局灶性癫痫发作频率不断增加,需要住院治疗,并持续静脉输注咪达唑仑:方法:引入考比司他(Cobicistat)作为药代动力学增效剂,以降低咪达唑仑的代谢清除率,从而增加暴露量并延长半衰期:结果:通过使用可比司他增效剂,患者可以从静脉注射咪达唑仑转为口服咪达唑仑,并以口服咪达唑仑治疗方案出院:结论:对于需要稳定咪达唑仑血药浓度的耐药性癫痫患者,可比司他能有效地从药代动力学角度增加咪达唑仑的暴露量。
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Therapeutic Drug Monitoring
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