Population Pharmacokinetic Modeling of Unbound Meropenem in Patients Undergoing Continuous Renal Replacement Therapy: An Observational Cohort Study.

IF 2.8 4区医学 Q2 MEDICAL LABORATORY TECHNOLOGY Therapeutic Drug Monitoring Pub Date : 2024-10-01 Epub Date: 2024-05-14 DOI:10.1097/FTD.0000000000001222

Kazutaka Oda, Hirofumi Jono, Hidenobu Kamohara, Hideyuki Saito

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Abstract

Background: The most effective dosing strategy of meropenem for patients undergoing continuous renal replacement therapy (CRRT) remains uncertain. This study aimed to analyze the population pharmacokinetics (popPKs) of unbound meropenem and establish an appropriate dosing approach.

Methods: This prospective study involved 19 patients for the development of a popPK model and an additional 10 for its validation. Ethical approval was obtained.

Results: The clearance of unbound meropenem was influenced by the sequential organ failure assessment (SOFA) score [=2.22 × (SOFA score/12)^1.88] and the effluent flow rate from the CRRT device, with an interindividual variability of 44.5%. The volume of distribution was affected by the simplified acute physiology score II [=23.1 × (simplified acute physiology score II/52)^1.54]. Monte Carlo simulations suggested meropenem doses ranging from 1.0 to 3.0 g/d using continuous infusion to achieve a target time above the 4 times of minimum inhibitory concentration of the unbound form (% f T >4×MIC ) of 100% for definitive therapy. For empirical therapy, a dose of 1.0 g/d using continuous infusion was recommended to target % f T >MIC of 100%.

Conclusions: This study developed a popPK model for unbound meropenem in patients undergoing CRRT and formulated dosing guidelines.

Clinical trial registration: UMIN000024321.

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连续接受肾脏替代疗法的患者体内未结合美罗培南的群体药代动力学模型：观察性队列研究

背景：对于接受持续肾脏替代疗法（CRRT）的患者，美罗培南最有效的剂量策略仍不确定。本研究旨在分析未结合的美罗培南的群体药代动力学（popPKs），并确定合适的给药方法：这项前瞻性研究有 19 名患者参与，用于建立 popPK 模型，另有 10 名患者参与验证。研究获得了伦理批准：结果：未结合的美罗培南的清除率受序贯器官衰竭评估（SOFA）评分[=2.22 × (SOFA 评分/12)^1.88]和 CRRT 设备流出流速的影响，个体间变异率为 44.5%。分布容积受简化急性生理学评分 II 的影响[=23.1 ×（简化急性生理学评分 II/52）^1.54]。蒙特卡洛模拟表明，美罗培南的剂量范围为 1.0 至 3.0 克/天，采用连续输注的方式，以达到高于非结合型最低抑菌浓度 4 倍的目标时间（%fT>4×MIC）100%，从而进行确定性治疗。对于经验性治疗，建议连续输注 1.0 克/天的剂量，以达到 %fT>MIC 100% 的目标：本研究为接受 CRRT 治疗的患者建立了非结合型美罗培南的 popPK 模型，并制定了用药指南：临床试验注册：UMIN000024321。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Therapeutic Drug Monitoring 医学-毒理学

CiteScore

5.00

自引率

8.00%

发文量

213

审稿时长

4-8 weeks

期刊介绍： Therapeutic Drug Monitoring is a peer-reviewed, multidisciplinary journal directed to an audience of pharmacologists, clinical chemists, laboratorians, pharmacists, drug researchers and toxicologists. It fosters the exchange of knowledge among the various disciplines–clinical pharmacology, pathology, toxicology, analytical chemistry–that share a common interest in Therapeutic Drug Monitoring. The journal presents studies detailing the various factors that affect the rate and extent drugs are absorbed, metabolized, and excreted. Regular features include review articles on specific classes of drugs, original articles, case reports, technical notes, and continuing education articles.