Abstract

Introduction: 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.

Areas covered: 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.

Expert opinion: Ganciclovir TDM is important to optimise 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

简介：巨细胞病毒（CMV）是一种机会感染性并发症，可以在异基因造血细胞移植（HCT）后发生。更昔洛韦及其更药前药缬更昔洛韦是该病治疗和预防的主要手段。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效用存在相互矛盾的证据。

涵盖的领域：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动力学特性的当前知识，并探讨同种异体HCT人群中更昔洛韦TDM的证据和挑战。

专家意见：更昔洛韦TDM对于优化药物动力学因素可变或对治疗反应不足的特定患者组的疗效最重要。然而，与治疗功效和毒性相关的明确的药代动力学暴露仍然难以捉摸。需要在特定患者组中进行前瞻性临床研究以阐明此问题。应该探索替代的TDM靶标，例如细胞内更昔洛韦三磷酸酯，因为它们可能被证明与临床结果和不良反应具有更好的相关性。随着CMV免疫监测的最新进展，将TDM与特定CMV免疫表型整合在预测模型中的新方法将通过将TDM与风险分层方法相结合来优化更昔洛韦剂量，将是有利的。