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优化更昔洛韦在异基因造血细胞移植受者中的应用 - 治疗药物监测的作用。

Optimization of Ganciclovir use in allogeneic hematopoietic cell transplant recipients - the role of therapeutic drug monitoring.

机构信息

Departments of Infectious Diseases, The National Centre for Infections in Cancer, Peter MacCallum Cancer Centre Melbourne, Australia.

Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Australia.

出版信息

Expert Rev Anti Infect Ther. 2021 Jun;19(6):707-718. doi: 10.1080/14787210.2021.1851193. Epub 2020 Dec 17.

Abstract

: Cytomegalovirus (CMV) is an opportunistic infectious complication that can occur after allogeneic hematopoietic cell transplantation (HCT). The mainstay of treatment and prevention of this infection is ganciclovir and its ester prodrug valganciclovir. There is conflicting evidence on the clinical utility of routine ganciclovir therapeutic drug monitoring (TDM) as a means to optimize treatment.: This review aims to describe the current knowledge of the pharmacokinetic and pharmacodynamic characteristics of ganciclovir and valganciclovir, and to explore the evidence and challenges surrounding ganciclovir TDM within the allogeneic HCT cohort.: Ganciclovir TDM is important to optimize efficacy in selected patient groups where there are variable pharmacokinetic factors or inadequate response to treatment. However, defined pharmacokinetic exposures which correlate with treatment efficacy and toxicity remain elusive. Prospective clinical studies in specific patient groups are required to clarify this issue. Alternative TDM targets such as the intracellular ganciclovir triphosphate should be explored as they may prove to have better correlation with clinical outcomes and adverse effects. With recent advances in CMV immune monitoring, novel approaches integrating TDM with specific CMV immune phenotyping in a predictive model will be advantageous in optimizing ganciclovir dosing by combining TDM with a risk stratification approach.

摘要

巨细胞病毒(CMV)是一种机会性感染并发症,可发生于异基因造血细胞移植(HCT)后。治疗和预防这种感染的主要方法是更昔洛韦及其酯前体缬更昔洛韦。关于常规更昔洛韦治疗药物监测(TDM)作为优化治疗手段的临床实用性,目前存在相互矛盾的证据。

本综述旨在描述更昔洛韦和缬更昔洛韦的药代动力学和药效学特征的现有知识,并探讨在异基因 HCT 队列中,更昔洛韦 TDM 的证据和挑战。

在存在可变药代动力学因素或对治疗反应不足的特定患者群体中,更昔洛韦 TDM 对于优化疗效非常重要。然而,与治疗效果和毒性相关的明确药代动力学暴露仍然难以捉摸。需要在特定患者群体中进行前瞻性临床研究来阐明这一问题。替代 TDM 目标,如细胞内更昔洛韦三磷酸,也应加以探索,因为它们可能与临床结果和不良反应有更好的相关性。随着 CMV 免疫监测的最新进展,将 TDM 与特定的 CMV 免疫表型相结合的新型方法在预测模型中进行整合,通过将 TDM 与风险分层方法相结合,将有利于优化更昔洛韦的剂量。

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