缬更昔洛韦在先天性巨细胞病毒感染婴儿中的药代动力学和药效学评价。

IF 2.8 4区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY
Therapeutic Drug Monitoring Pub Date : 2025-06-01 Epub Date: 2024-09-04 DOI:10.1097/FTD.0000000000001257
Kotaro Itohara, Kazuhiro Yamamoto, Shunsuke Fujinaka, Mari Hashimoto, Naoki Tamura, Yumi Kitahiro, Tomohiro Omura, Kazumichi Fujioka, Ikuko Yano
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引用次数: 0

摘要

背景:缬更昔洛韦(VGCV)治疗先天性巨细胞病毒(CMV)感染,剂量为16mg /kg,每日2次,疗程6个月。在治疗期间,大约20%的患者出现3级或更高级别的中性粒细胞减少症。目前,关于更昔洛韦(VGCV的一种活性代谢物)在婴儿中的药代动力学和药效学信息有限。本研究探讨了更昔洛韦浓度与中性粒细胞减少的关系,并建立了更昔洛韦在先天性CMV感染婴儿中的群体药代动力学(PPK)模型。方法:纳入2017年7月至2021年1月期间口服VGCV治疗有症状的先天性巨细胞病毒感染的日本婴儿。观察更昔洛韦浓度与中性粒细胞计数之间的关系。采用PPK分析评价影响更昔洛韦药代动力学的协变量。结果:分析了8例患者27份更昔洛韦血清样本。更昔洛韦槽浓度与中性粒细胞计数呈中度负相关。PPK模型分析显示,经经验性体重异速缩放校正后,经后年龄(PMA)影响更昔洛韦的全身清除率。根据PMA和体重,计算更昔洛韦40 ~ 60 mcg·h·mL -1在0 ~ 24 h浓度-时间曲线下达到靶面积的图。结论:明确了婴儿中性粒细胞计数与更昔洛韦谷浓度的关系。PPK模型显示,低PMA患者应减少VGCV剂量以达到靶暴露。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Pharmacokinetic and Pharmacodynamic Assessment of Valganciclovir in Infants With Congenital Cytomegalovirus Infection.

Background: Valganciclovir (VGCV) is administered at a dose of 16 mg/kg 2 times daily for 6 months to treat symptomatic congenital cytomegalovirus (CMV) infections. During the treatment period, approximately 20% of the patients developed grade 3 or higher neutropenia. Currently, information on the pharmacokinetics and pharmacodynamics of ganciclovir, an active metabolite of VGCV, in infants is limited. In the current study, the relationship between ganciclovir concentration and neutropenia was investigated, and a population pharmacokinetic (PPK) model of ganciclovir in infants with symptomatic congenital CMV infection was developed.

Methods: Japanese infants who were prescribed oral VGCV for symptomatic congenital CMV infections between July 2017 and January 2021 were included. The relationship between the observed trough ganciclovir concentrations and neutrophil counts was examined. PPK analysis was performed to evaluate the covariates affecting the pharmacokinetics of ganciclovir.

Results: Twenty-seven ganciclovir serum samples from 8 patients were analyzed. A moderate negative correlation was observed between the observed trough ganciclovir concentration and neutrophil count. PPK model analysis showed that postmenstrual age (PMA) affected the total body clearance of ganciclovir after correcting for the empirical allometric scaling of body weight. Based on PMA and body weight, a nomogram to achieve the target area under the concentration-time curve from 0 to 24 hours of 40-60 mcg·h·mL -1 of ganciclovir was calculated.

Conclusions: The relationship between neutrophil count and ganciclovir trough concentration in infants was clarified. The PPK model showed that the dose of VGCV should be reduced in patients with a low PMA to achieve target exposure.

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来源期刊
Therapeutic Drug Monitoring
Therapeutic Drug Monitoring 医学-毒理学
CiteScore
5.00
自引率
8.00%
发文量
213
审稿时长
4-8 weeks
期刊介绍: Therapeutic Drug Monitoring is a peer-reviewed, multidisciplinary journal directed to an audience of pharmacologists, clinical chemists, laboratorians, pharmacists, drug researchers and toxicologists. It fosters the exchange of knowledge among the various disciplines–clinical pharmacology, pathology, toxicology, analytical chemistry–that share a common interest in Therapeutic Drug Monitoring. The journal presents studies detailing the various factors that affect the rate and extent drugs are absorbed, metabolized, and excreted. Regular features include review articles on specific classes of drugs, original articles, case reports, technical notes, and continuing education articles.
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