A Systematic Review of Linezolid Pharmacokinetics/Pharmacodynamics in Patients Undergoing Continuous Renal Replacement Therapy: Does One Size Fit All?

IF 2.1 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Yao Liu, Xu-Hua Ge, Hong-Li Guo, Feng Chen, Yong Zhang, Jing Xu, Xing Ji, Hong-Jun Miao
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引用次数: 1

Abstract

Background: Selection of the optimal antimicrobial posology in critically ill patients remains a challenge, especially in patients with sepsis who undergo continuous renal replacement therapy (CRRT). This systematic review aimed to analyze factors that influence the extracorporeal removal of linezolid.

Methods: A comprehensive search was performed to identify studies published up to March 2022 in PubMed, MEDLINE and EMBASE databases. Studies involving adults receiving CRRT and treatment with linezolid were considered eligible if the CRRT setting and linezolid's pharmacokinetic parameters were clearly mentioned.

Results: Six out of 110 potentially relevant studies were included. A total of 101 treatments were identified among 97 enrolled patients. Our analysis showed that continuous veno-venous hemodiafiltration (CVVHDF) was the most frequential used modality (52 cases). Despite distribution volume, the clearance (CL) of linezolid in these studies had large variability. Extracorporeal linezolid removal may be markedly impacted by CRRT dose. There is significant between-subject variability in the probability of pharmacokinetics-pharmacodynamics (PK-PD) target attainment of patients treated with CRRT.

Conclusion: Dose adjustment, shortening the dosing interval, and continuous infusion were proposed as regimen optimization. Therapeutic drug monitoring is recommended due to the high variability of linezolid exposure among patients with CRRT, specifically for those whose bodyweight is high, renal function is preserved, and the MIC of infection bacteria is above 2 μg/mL.

连续肾替代治疗患者利奈唑胺药代动力学/药效学的系统评价:一个标准适合所有患者吗?
背景:在危重患者中选择最佳的抗菌药物仍然是一个挑战,特别是在接受持续肾脏替代治疗(CRRT)的脓毒症患者中。本系统综述旨在分析影响利奈唑胺体外去除的因素。方法:对PubMed、MEDLINE和EMBASE数据库中截至2022年3月发表的研究进行全面检索。如果明确提及CRRT的设置和利奈唑胺的药代动力学参数,则接受CRRT和利奈唑胺治疗的成人研究被认为是合格的。结果:110项可能相关的研究中有6项被纳入。在97名入组患者中共确定了101种治疗方法。我们的分析显示,连续静脉-静脉血液滤过(CVVHDF)是最常用的方式(52例)。尽管分布体积大,利奈唑胺清除率(CL)在这些研究中有很大的变异性。体外利奈唑胺去除可能受到CRRT剂量的显著影响。接受CRRT治疗的患者的药代动力学-药效学(PK-PD)目标达到的概率在受试者之间存在显著差异。结论:调整剂量、缩短给药间隔、持续输注是优化方案。由于在CRRT患者中利奈唑胺暴露的高度变异性,特别是那些体重高、肾功能保存、感染细菌MIC高于2 μg/mL的患者,建议进行治疗性药物监测。
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来源期刊
Current drug metabolism
Current drug metabolism 医学-生化与分子生物学
CiteScore
4.30
自引率
4.30%
发文量
81
审稿时长
4-8 weeks
期刊介绍: Current Drug Metabolism aims to cover all the latest and outstanding developments in drug metabolism, pharmacokinetics, and drug disposition. The journal serves as an international forum for the publication of full-length/mini review, research articles and guest edited issues in drug metabolism. Current Drug Metabolism is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the most important developments. The journal covers the following general topic areas: pharmaceutics, pharmacokinetics, toxicology, and most importantly drug metabolism. More specifically, in vitro and in vivo drug metabolism of phase I and phase II enzymes or metabolic pathways; drug-drug interactions and enzyme kinetics; pharmacokinetics, pharmacokinetic-pharmacodynamic modeling, and toxicokinetics; interspecies differences in metabolism or pharmacokinetics, species scaling and extrapolations; drug transporters; target organ toxicity and interindividual variability in drug exposure-response; extrahepatic metabolism; bioactivation, reactive metabolites, and developments for the identification of drug metabolites. Preclinical and clinical reviews describing the drug metabolism and pharmacokinetics of marketed drugs or drug classes.
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