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临床实践中伊曲康唑游离分数的高度变异性：重新考虑药代动力学/药效学目标和折点的呼吁。

High Variability in Isavuconazole Unbound Fraction in Clinical Practice: A Call to Reconsider Pharmacokinetic/Pharmacodynamic Targets and Breakpoints.

机构信息

Department of Pharmacy, Radboud university Medical Center, Radboud Institute for Medical Innovations, Geert Grooteplein-Zuid 10, Postbox 9101, 6500 HB, Nijmegen, The Netherlands.

Radboud University Medical Center-Canisius Wilhelmina Ziekenhuis Center of Expertise for Mycology, Nijmegen, The Netherlands.

出版信息

Clin Pharmacokinet. 2023 Dec;62(12):1695-1699. doi: 10.1007/s40262-023-01311-w. Epub 2023 Oct 11.

DOI:10.1007/s40262-023-01311-w
PMID:37819504
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10684614/
Abstract

Isavuconazole exposure-response relationships have been studied with a focus on total rather than unbound exposure, assuming a constant unbound fraction of 1%. We observed a median (range) unbound fraction of 1.59% (0.42-5.30%) in patients. This highly variable protein binding asks for re-evaluation of current pharmacokinetic and pharmacodynamic targets for isavuconazole.

摘要

伊曲康唑的暴露-反应关系研究主要集中在总暴露量上，而非游离暴露量，假设游离分数为 1%不变。我们观察到患者的游离分数中位数（范围）为 1.59%（0.42-5.30%）。这种高度可变的蛋白结合要求重新评估伊曲康唑目前的药代动力学和药效学靶标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ae2/10684614/884d266ae4d3/40262_2023_1311_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ae2/10684614/884d266ae4d3/40262_2023_1311_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ae2/10684614/884d266ae4d3/40262_2023_1311_Fig1_HTML.jpg

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Clin Microbiol Infect. 2018 May;24 Suppl 1:e1-e38. doi: 10.1016/j.cmi.2018.01.002. Epub 2018 Mar 12.
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