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血液吸附疗法中药物吸附曲线的体外评估

In vitro Assessment of Drug Adsorption Profiles during Hemoadsorption Therapy.

作者信息

Körtge Andreas, Kamper Christoph, Klinkmann Gerd, Wasserkort Reinhold, Mitzner Steffen

机构信息

Department of Extracorporeal Therapy Systems, Fraunhofer Institute for Cell Therapy and Immunology IZI, Rostock, Germany.

Division of Nephrology, Center for Internal Medicine, Rostock University Medical Center, Rostock, Germany.

出版信息

Blood Purif. 2025 Mar 20:1-8. doi: 10.1159/000545120.

Abstract

INTRODUCTION

The use of hemoadsorption devices is increasingly gaining impact as an adjunct therapy for various critical conditions in ICU patients, including systemic hyperinflammation, cytokine release syndrome, sepsis, and more. A key concern in this therapy is its impact on the plasma levels of concurrently administered drugs, which could potentially be reduced to subtherapeutic levels, affecting patient care. The present study investigates the adsorption behavior of various drugs in an in vitro hemoadsorption model using human whole blood, aiming to provide insights for optimizing drug dosing during hemoadsorption therapy.

METHODS

The study assessed the removal rates and clearances of several drugs, namely, apixaban, argatroban, carbamazepine, oxcarbazepine, lamotrigine, phenytoin, valproate, levosimendan, methylene blue, and metformin, by circulating the blood through CytoSorb adsorbers in an in vitro setup.

RESULTS

Significant removal (75 to 100% of the initial concentration) and high initial plasma clearances (approximately 10-25 mL/min) were observed for most of the tested drugs within the first 30-60 min of recirculation. Lower removal rates and clearances were noted for valproate (approximately 40% and 5 mL/min) and metformin (approximately 15% and 1 mL/min).

CONCLUSION

The findings indicate considerable differences in the adsorption of the tested drugs and should be confirmed by additional in vivo studies with careful monitoring of drug levels throughout the course of therapy. Understanding the in vivo dynamics is crucial for adjusting dosages appropriately during hemoadsorption use to ensure therapeutic efficacy and patient safety.

摘要

引言

血液吸附装置作为重症监护病房(ICU)患者各种危急病症的辅助治疗方法,其应用越来越广泛,这些病症包括全身炎症反应、细胞因子释放综合征、败血症等。这种治疗方法的一个关键问题是其对同时使用药物血浆水平的影响,药物血浆水平可能会降至亚治疗水平,从而影响患者的治疗。本研究使用人全血在体外血液吸附模型中研究了各种药物的吸附行为,旨在为优化血液吸附治疗期间的药物剂量提供见解。

方法

该研究通过在体外装置中使血液流经CytoSorb吸附器,评估了几种药物的清除率,这些药物分别是阿哌沙班、阿加曲班、卡马西平、奥卡西平、拉莫三嗪、苯妥英、丙戊酸盐、左西孟旦、亚甲蓝和二甲双胍。

结果

在再循环的最初30 - 60分钟内,大多数受试药物观察到显著清除(初始浓度的75%至100%)和较高的初始血浆清除率(约10 - 25 mL/分钟)。丙戊酸盐(约40%和5 mL/分钟)和二甲双胍(约15%和1 mL/分钟)的清除率和清除速率较低。

结论

研究结果表明受试药物的吸附存在显著差异,应通过额外的体内研究进行确认,并在整个治疗过程中仔细监测药物水平。了解体内动力学对于在血液吸附治疗期间适当调整剂量以确保治疗效果和患者安全至关重要。

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