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更昔洛韦和缬更昔洛韦在儿童巨细胞病毒感染中的临床药代动力学和药效学。

Clinical pharmacokinetics and pharmacodynamics of ganciclovir and valganciclovir in children with cytomegalovirus infection.

机构信息

University of Utah School of Medicine, Division of Clinical Pharmacology, Department of Pediatrics , 295 Chipeta Way, Salt Lake City, UT 84108 , USA +1 801 587 7404 ; +1 801 585 9410 ;

出版信息

Expert Opin Drug Metab Toxicol. 2015 Feb;11(2):205-19. doi: 10.1517/17425255.2015.988139. Epub 2014 Nov 27.

Abstract

INTRODUCTION

Among infants and immunocompromised children cytomegalovirus (CMV) is associated with significant morbidity and mortality.

AREAS COVERED

This review describes the clinical pharmacokinetics and pharmacodynamics of ganciclovir and valganciclovir for the treatment and prevention of CMV infection in children.

EXPERT OPINION

A 24-h ganciclovir area under the concentration versus time curve (AUC₀₋₂₄) of 40 - 60 μg h/ml decreased the risk of CMV infection for adults undergoing CMV prophylaxis. For adults undergoing treatment for active CMV disease, a target AUC₀₋₁₂ of 40 - 60 μg h/ml has been suggested. The applicability of these targets to children remains uncertain; however, with the most sophisticated dosing regimens developed to date only 21% of patients are predicted to reach these targets. Moving forward, identification of optimal pediatric ganciclovir and valganciclovir dosing regimens may involve the use of an externally validated pediatric population pharmacokinetic model for empirical dosing, an optimal sampling strategy for collecting a minimal number of blood samples for each patient and Bayesian updating of the dosing regimen based on an individual patient's pharmacokinetic profile.

摘要

简介

在婴儿和免疫功能低下的儿童中,巨细胞病毒(CMV)与较高的发病率和死亡率相关。

涵盖领域

本综述描述了更昔洛韦和缬更昔洛韦在儿童中治疗和预防 CMV 感染的临床药代动力学和药效动力学。

专家意见

对于接受 CMV 预防的成人,24 小时更昔洛韦浓度-时间曲线下面积(AUC₀₋₂₄)为 40-60μg h/ml 可降低 CMV 感染的风险。对于接受 CMV 活动性疾病治疗的成人,建议的目标 AUC₀₋₁₂为 40-60μg h/ml。这些目标对儿童的适用性仍不确定;然而,迄今为止,最复杂的给药方案仅预测 21%的患者能够达到这些目标。未来,确定最佳的儿童更昔洛韦和缬更昔洛韦给药方案可能需要使用经过外部验证的儿科群体药代动力学模型进行经验性给药,采用最优的采样策略为每个患者采集尽可能少的血样,并根据个体患者的药代动力学特征对给药方案进行贝叶斯更新。

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