Therapeutic drug monitoring of amikacin in preterm and term neonates with late‐onset sepsis. Can saliva samples replace plasma samples?

Author:

Samb Amadou1ORCID,Sinkeler Fleur1ORCID,Bijleveld Yuma A.1,van Kaam Anton2,de Haan Timo R.2,Mathôt Ron1

Affiliation:

1. Pharmacy and Clinical Pharmacology Amsterdam UMC location University of Amsterdam Meibergdreef 9 Amsterdam The Netherlands

2. Amsterdam UMC location University of Amsterdam Neonatology, Meibergdreef 9 Amsterdam The Netherlands

Abstract

Amikacin is an aminoglycoside antibiotic that is frequently used for the treatment of neonatal late‐onset sepsis, for which therapeutic drug monitoring (TDM) is advised. In order to decrease the TDM associated burden of plasma sampling, a noninvasive TDM method using saliva samples was investigated.MethodsThis was a prospective single‐centre, observational feasibility study with 23 premature and term neonates from whom up to 8 saliva samples were collected, together with residual plasma from clinical routine. Amikacin concentrations in saliva and plasma were quantified with liquid chromatography–tandem mass spectrometry. A population pharmacokinetic analysis was performed to develop an integrated pharmacokinetic model of amikacin in plasma and saliva and for the identification of covariates. TDM performance of different sampling regimens was evaluated using Monte Carlo simulations in a fictional cohort of representative neonates (n = 10 000).ResultsAmikacin could be detected in saliva and a saliva compartment was appended to a 2‐compartment plasma model. First‐order absorption (k13) of the saliva compartment was 0.0345 h−1 with an interindividual variability of 45.3%. The rate of first‐order elimination (k30) was 0.176 h−1. Postmenstrual age had a significant negative covariate effect on k13, with an exponent of −4.3. Target attainment increased from 77.6 to 79.2% and from 79.9 to 83.2% using 1–to 5 saliva samples or 1–5 plasma samples, respectively.ConclusionTDM of amikacin using saliva samples results in target attainment comparable to plasma samples and may be beneficial for (premature) neonates with late‐onset sepsis.

Funder

Janivo Stichting

Amsterdam University Medical Centers

Publisher

Wiley

Subject

Pharmacology (medical),Pharmacology

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3