Exposure-Response of Posaconazole Used for Prophylaxis Against Invasive Fungal Infections: Evaluating the Need to Adjust Doses Based on Drug Concentrations in Plasma
Exposure-Response of Posaconazole Used for Prophylaxis Against Invasive Fungal Infections: Evaluating the Need to Adjust Doses Based on Drug Concentrations in Plasma
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DOI：
10.1038/clpt.2010.64
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发表时间：
2010-07-01
影响因子：
6.7
通讯作者：
Gobburu, J. V. S.
中科院分区：
文献类型：
--
作者：
Jang, S. H.;Colangelo, P. M.;Gobburu, J. V. S.
本文根据美国食品药品监督管理局（FDA）对泊沙康唑口服混悬液（POS）预防侵袭性真菌感染（IFIs）的两项随机、活性对照临床研究的临床药理学评价，报告POS预防IFIs的疗效-反应（E-R）关系。泊沙康唑200 mg每日三次（t.i.d.）给药后，泊沙康唑平均稳态血浆浓度（C（avg））范围为22 - 3，650 ng/ml。在一项双盲、随机临床试验中，C（avg）的四分位数范围（中点值为289、736、1，239和2，607 ng/ml）的临床失败率分别为44%、21%、18%和18%，表明C（avg）与临床失败率之间呈负相关。C（avg）与泊沙康唑相关的主要不良事件之间无显著相关性。测定泊沙康唑的血浆浓度将有助于评估POS剂量调整的需要（例如，增加POS剂量）或改用另一种全身性抗真菌药物，从而提高预防IFIs的有效性。
The purpose of this article is to report the exposure-response (E-R) relationship of posaconazole oral suspension (POS) for prophylaxis against invasive fungal infections (IFIs), on the basis of the us Food and Drug administration (FDA) clinical pharmacology review of two randomized, active-controlled clinical studies. posaconazole average steady-state plasma concentrations (C(avg)) ranged from 22 to 3,650 ng/ml after administration of POS 200 mg three times daily (t.i.d.). in a double-blind, randomized clinical trial, the quartile ranges of C(avg) with midpoint values of 289, 736, 1,239, and 2,607 ng/ml had clinical failure rates of 44, 21, 18, and 18%, respectively, indicating an inverse association between C(avg) and clinical failure rate. There were no significant relationships between C(avg) and posaconazole-related major adverse events. Determining posaconazole concentrations in plasma will aid in assessing the need for either POS dose adjustment (e.g., increasing the POS dose) or switching to another systemic antifungal drug, thereby improving the effectiveness of prophylaxis against IFIs.