Population pharmacokinetics and dosing optimisation of imipenem in critically ill patients.

IF 1.6 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Jing Bai, Aiping Wen, Zhe Li, Xingang Li, Meili Duan
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引用次数: 0

Abstract

Objective: The objective of this study was to explore factors that affect the clearance of imipenem in critically ill patients and to provide a dosing regimen for such patients.

Methods: A prospective open-label study enrolled 51 critically ill patients with sepsis. Patients were between the ages of 18 and 96. Blood samples were collected in duplicate before (0 hour) and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours after imipenem administration. The plasma imipenem concentration was determined by the high-performance liquid chromatography-ultraviolet detection (HPLC-UV) method. A population pharmacokinetic (PPK) model was developed using nonlinear mixed-effects modelling methods to identify covariates. Monte Carlo simulations were performed using the final PPK model to explore the effect of different dosing regimens on the probability of target attainment (PTA).

Results: The imipenem concentration data were best described by a two-compartment model. Creatinine clearance (CrCl, mL/min) was a covariate that affected central clearance (CLc). Patients were divided into four subgroups based on different CrCl rates. Monte Carlo simulations were performed to assess the PTA differences between empirical dosing regimens (0.5 g every 6 hours (q6h), 0.5 g every 8 hours (q8h), 0.5 g every 12 hours (q12h), 1 g every 6 hours (q6h), 1 g every 8 hours (q8h), and 1 g every 12 hours (q12h)) and to determine the target achievement rate covariate.

Conclusion: This study identified covariates for CLc, and the proposed final model can be used to guide clinicians administering imipenem in this particular patient population.

重症患者亚胺培南的群体药代动力学和剂量优化。
研究目的本研究旨在探讨影响重症患者亚胺培南清除率的因素,并为此类患者提供给药方案:一项前瞻性开放标签研究共招募了 51 名脓毒症重症患者。患者年龄在 18 岁至 96 岁之间。在亚胺培南用药前(0 小时)和用药后 0.5、1、1.5、2、3、4、6 和 8 小时分别采集一式两份的血液样本。采用高效液相色谱-紫外检测(HPLC-UV)法测定血浆中亚胺培南的浓度。采用非线性混合效应建模方法建立了群体药代动力学(PPK)模型,以确定协变量。利用最终的 PPK 模型进行了蒙特卡罗模拟,以探讨不同给药方案对达标概率(PTA)的影响:结果:亚胺培南浓度数据用两室模型进行了最佳描述。肌酐清除率(CrCl,毫升/分钟)是影响中心清除率(CLc)的协变量。根据不同的 CrCl 率将患者分为四个亚组。通过蒙特卡罗模拟评估了经验给药方案(每 6 小时 0.5 克(q6h)、每 8 小时 0.5 克(q8h)、每 12 小时 0.5 克(q12h)、每 6 小时 1 克(q6h)、每 8 小时 1 克(q8h)和每 12 小时 1 克(q12h))之间的 PTA 差异,并确定了目标达成率的协变量:本研究确定了CLc的协变量,提出的最终模型可用于指导临床医生在这一特殊患者群体中使用亚胺培南。
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
CiteScore
3.40
自引率
5.90%
发文量
104
审稿时长
6-12 weeks
期刊介绍: European Journal of Hospital Pharmacy (EJHP) offers a high quality, peer-reviewed platform for the publication of practical and innovative research which aims to strengthen the profile and professional status of hospital pharmacists. EJHP is committed to being the leading journal on all aspects of hospital pharmacy, thereby advancing the science, practice and profession of hospital pharmacy. The journal aims to become a major source for education and inspiration to improve practice and the standard of patient care in hospitals and related institutions worldwide. EJHP is the only official journal of the European Association of Hospital Pharmacists.
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