针对肾功能不全的医院获得性肺炎患者的利奈唑胺群体药代动力学/药效学研究

IF 4.7 2区医学 Q1 CHEMISTRY, MEDICINAL

Drug Design, Development and Therapy Pub Date : 2024-11-08 eCollection Date: 2024-01-01 DOI:10.2147/DDDT.S474470

Jinhui Xu, Xianglong Chen, Qian Zhang, Zhiwei Zhuang, Yunlong Yuan, Lufen Duan, Lu Shi, Chenqi Zhu, JingJing Li, Jian Lu, Yanxia Yu, Lian Tang

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引用次数: 0

摘要

目的：对于由革兰氏阳性菌引起的医院获得性肺炎（HAP）患者和肾功能不全患者，最佳治疗策略仍具有挑战性。本研究旨在比较利奈唑胺与替考拉宁在肾功能不全的 HAP 患者中的疗效，并探讨利奈唑胺的最佳剂量策略：该回顾性研究纳入了2018年7月至2023年8月期间在苏州市立医院接受静脉注射利奈唑胺或替考拉宁治疗的成人患者。在药效学比较研究中，比较了替考拉宁与利奈唑胺治疗文件革兰氏阳性菌和肾功能不全的HAP患者的有效性、安全性和达到目标谷浓度（Cmin）。在群体药代动力学（PPK）分析中，使用了专门从肾功能不全的HAP患者中收集的利奈唑胺浓度，并使用蒙特卡洛模拟法研究了最佳剂量策略：利奈唑胺治疗患者的细菌根除率高于替考拉宁治疗患者（88.5% vs 63.4%，P < 0.001）。利奈唑胺组中出现至少一种不良反应的患者比例更高（42.0% vs 25.0%，P = 0.025）。利奈唑胺组达到超治疗浓度的 Cmin 明显多于利奈唑胺组，达到治疗浓度的 Cmin 明显少于利奈唑胺组（调整后 P <0.05）。共有来自 166 名肾功能不全患者的 207 份利奈唑胺浓度资料可用于 PPK 分析。年龄和肌酐清除率（CrCL）被认为是影响清除率的重要协变量。模拟结果显示，CrCL为60或45 mL/min的患者，300 mg q12h可提供最佳暴露量；CrCL为30或15 mL/min的患者，建议200 mg q12h：结论：与替考拉宁治疗的患者相比，利奈唑胺治疗的HAP和肾功能不全患者具有更高的细菌根除率、超治疗暴露和不良反应。肾功能不全患者减少利奈唑胺的剂量可提高达到最佳暴露的概率。

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Population Pharmacokinetic/Pharmacodynamic Study of Linezolid in Hospital-Acquired Pneumonia Patients with Renal Insufficiency.

Purpose: The optimal treatment strategy in patients with hospital-acquired pneumonia (HAP) due to Gram-positive bacteria and renal insufficiency remains challenging. The objective of this study was to compare the outcomes of linezolid versus teicoplanin in HAP patients with renal insufficiency and to explore optimal dosage strategy for linezolid.

Methods: The retrospective study enrolled adult patients treated with intravenous linezolid or teicoplanin at Suzhou Municipal Hospital between July 2018 and August 2023. For the comparative pharmacodynamic study, effectiveness, safety and target attainment of trough concentration (C_min) for teicoplanin versus linezolid treatment in HAP patients with document Gram-positive bacteria and renal insufficiency were compared. For the population pharmacokinetics (PPK) analyses, linezolid concentrations collected exclusively from HAP patients with renal insufficiency were used and the optimal dosage strategy was investigated using Monte Carlo simulations.

Results: Linezolid-treated patients had a higher bacterial eradication rate than teicoplanin-treated patients (88.5% vs 63.4%, P < 0.001). A higher proportion of patients in the linezolid group experienced at least one adverse reaction (42.0% vs 25.0%, P = 0.025). Significantly more supratherapeutic C_min, less therapeutic C_min were achieved in the linezolid group (adjusted P < 0.05). A total of 207 linezolid concentrations from 166 patients with renal insufficiency were available for the PPK analysis. Age and creatinine clearance (CrCL) were identified as significant covariates that influenced clearance. Simulations show that 300 mg q12h provide the optimal exposure in patients with a CrCL of 60 or 45 mL/min, and 200 mg q12h was recommended for patients with a CrCL of 30 or 15 mL/min.

Conclusion: Linezolid-treated patients with HAP and renal insufficiency had higher bacterial eradication rates, supratherapeutic exposure and adverse reactions than teicoplanin-treated patients. Linezolid dose reduction in patients with renal insufficiency improved the probability of achieving optimal exposure.

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来源期刊

Drug Design, Development and Therapy CHEMISTRY, MEDICINAL-PHARMACOLOGY & PHARMACY

CiteScore

9.00

自引率

0.00%

发文量

382

审稿时长

>12 weeks

期刊介绍： Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications. The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas. Specific topics covered by the journal include: Drug target identification and validation Phenotypic screening and target deconvolution Biochemical analyses of drug targets and their pathways New methods or relevant applications in molecular/drug design and computer-aided drug discovery* Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes) Structural or molecular biological studies elucidating molecular recognition processes Fragment-based drug discovery Pharmaceutical/red biotechnology Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products** Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing) Preclinical development studies Translational animal models Mechanisms of action and signalling pathways Toxicology Gene therapy, cell therapy and immunotherapy Personalized medicine and pharmacogenomics Clinical drug evaluation Patient safety and sustained use of medicines.