Dataset Information

A neonatal amikacin covariate model can be used to predict ontogeny of other drugs eliminated through glomerular filtration in neonates.

ABSTRACT: Recently, a covariate model characterizing developmental changes in clearance of amikacin in neonates has been developed using birth bodyweight and postnatal age. The aim of this study was to evaluate whether this covariate model can be used to predict maturation in clearance of other renally excreted drugs.Five different neonatal datasets were available on netilmicin, vancomycin, tobramycin and gentamicin. The extensively validated covariate model for amikacin clearance was used to predict clearance of these drugs. In addition, independent reference models were developed based on a systematic covariate analysis.The descriptive and predictive properties of the models developed using the amikacin covariate model were good, and fairly similar to the independent reference models (goodness-of-fit plots, NPDE). Moreover, similar clearance values were obtained for both approaches. Finally, the same covariates as in the covariate model of amikacin, i.e. birth bodyweight and postnatal age, were identified on clearance in the independent reference models.This study shows that pediatric covariate models may contain physiological information since information derived from one drug can be used to describe other drugs. This semi-physiological approach may be used to optimize sparse data analysis and to derive individualized dosing algorithms for drugs in children.

SUBMITTER: De Cock RF

PROVIDER: S-EPMC5565484 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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A neonatal amikacin covariate model can be used to predict ontogeny of other drugs eliminated through glomerular filtration in neonates.

De Cock Roosmarijn F W RF Allegaert Karel K Sherwin Catherine M T CM Nielsen Elisabet I EI de Hoog Matthijs M van den Anker Johannes N JN Danhof Meindert M Knibbe Catherijne A J CA

Pharmaceutical research 20130925 3

<h4>Purpose</h4>Recently, a covariate model characterizing developmental changes in clearance of amikacin in neonates has been developed using birth bodyweight and postnatal age. The aim of this study was to evaluate whether this covariate model can be used to predict maturation in clearance of other renally excreted drugs.<h4>Methods</h4>Five different neonatal datasets were available on netilmicin, vancomycin, tobramycin and gentamicin. The extensively validated covariate model for amikacin cl ...[more]

PMID: 24065592

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Project description:Inflammatory activation and/or dysfunction of the glomerular endothelium triggers proteinuria in many systemic and localized vascular disorders. Among them are the thrombotic microangiopathies, many forms of glomerulonephritis, and acute inflammatory episodes like sepsis and COVID-19 illness. Another example is the chronic endothelial dysfunction that develops in cardiovascular disease and in metabolic disorders like diabetes. While the glomerular endothelium is a porous sieve that filters prodigious amounts of water and small solutes, it also bars the bulk of albumin and large plasma proteins from passing into the glomerular filtrate. This endothelial barrier function is ascribed predominantly to the endothelial glycocalyx with its endothelial surface layer, that together form a relatively thick, mucinous coat composed of glycosaminoglycans, proteoglycans, glycolipids, sialomucins and other glycoproteins, as well as secreted and circulating proteins. The glycocalyx/endothelial surface layer not only covers the glomerular endothelium; it extends into the endothelial fenestrae. Some glycocalyx components span or are attached to the apical endothelial cell plasma membrane and form the formal glycocalyx. Other components, including small proteoglycans and circulating proteins like albumin and orosomucoid, form the endothelial surface layer and are bound to the glycocalyx due to weak intermolecular interactions. Indeed, bound plasma albumin is a major constituent of the endothelial surface layer and contributes to its barrier function. A role for glomerular endothelial cells in the barrier of the glomerular capillary wall to protein filtration has been demonstrated by many elegant studies. However, it can only be fully understood in the context of other components, including the glomerular basement membrane, the podocytes and reabsorption of proteins by tubule epithelial cells. Discovery of the precise mechanisms that lead to glycocalyx/endothelial surface layer disruption within glomerular capillaries will hopefully lead to pharmacological interventions that specifically target this important structure.

Dataset Information

A neonatal amikacin covariate model can be used to predict ontogeny of other drugs eliminated through glomerular filtration in neonates.

Publications

A neonatal amikacin covariate model can be used to predict ontogeny of other drugs eliminated through glomerular filtration in neonates.

Similar Datasets

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