Advancement of pharmacokinetic models of iohexol in patients aged 70 years or older with impaired kidney function

Abstract Plasma clearance of iohexol is a pivotal metric to quantify glomerular filtration rate (GFR), but the optimal timing and frequency of plasma sampling remain to be assessed. In this study, we evaluated the impact of a Bayesian estimation procedure on iohexol clearance estimates, and we ident...

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Autores principales:	Max Taubert, Elke Schaeffner, Peter Martus, Markus van der Giet, Uwe Fuhr, Amina Lösment, Natalie Ebert
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f6a1f16dee5843c097c784d47edb7de6
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spelling	oai:doaj.org-article:f6a1f16dee5843c097c784d47edb7de62021-11-28T12:21:23ZAdvancement of pharmacokinetic models of iohexol in patients aged 70 years or older with impaired kidney function10.1038/s41598-021-01892-12045-2322https://doaj.org/article/f6a1f16dee5843c097c784d47edb7de62021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-01892-1https://doaj.org/toc/2045-2322Abstract Plasma clearance of iohexol is a pivotal metric to quantify glomerular filtration rate (GFR), but the optimal timing and frequency of plasma sampling remain to be assessed. In this study, we evaluated the impact of a Bayesian estimation procedure on iohexol clearance estimates, and we identified an optimal sampling strategy based on data in individuals aged 70+. Assuming a varying number of random effects, we re-estimated previously developed population pharmacokinetic two- and three-compartment models in a model development group comprising 546 patients with iohexol concentration data up to 300 min post injection. Model performance and optimal sampling times were assessed in an evaluation group comprising 104 patients with reduced GFR and concentration data up to 1440 min post injection. Two- and three-compartment models with random effects for all parameters overestimated clearance values (bias 5.07 and 4.40 mL/min, respectively) and underpredicted 24-h concentrations (bias − 14.5 and − 12.0 µg/ml, respectively). Clearance estimates improved distinctly when limiting random effects of the three-compartment model to clearance and central volume of distribution. Two blood samples, one early and one 300 min post injection, were sufficient to estimate iohexol clearance. A simplified three-compartment model is optimal to estimate iohexol clearance in elderly patients with reduced GFR.Max TaubertElke SchaeffnerPeter MartusMarkus van der GietUwe FuhrAmina LösmentNatalie EbertNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Max Taubert Elke Schaeffner Peter Martus Markus van der Giet Uwe Fuhr Amina Lösment Natalie Ebert Advancement of pharmacokinetic models of iohexol in patients aged 70 years or older with impaired kidney function
description	Abstract Plasma clearance of iohexol is a pivotal metric to quantify glomerular filtration rate (GFR), but the optimal timing and frequency of plasma sampling remain to be assessed. In this study, we evaluated the impact of a Bayesian estimation procedure on iohexol clearance estimates, and we identified an optimal sampling strategy based on data in individuals aged 70+. Assuming a varying number of random effects, we re-estimated previously developed population pharmacokinetic two- and three-compartment models in a model development group comprising 546 patients with iohexol concentration data up to 300 min post injection. Model performance and optimal sampling times were assessed in an evaluation group comprising 104 patients with reduced GFR and concentration data up to 1440 min post injection. Two- and three-compartment models with random effects for all parameters overestimated clearance values (bias 5.07 and 4.40 mL/min, respectively) and underpredicted 24-h concentrations (bias − 14.5 and − 12.0 µg/ml, respectively). Clearance estimates improved distinctly when limiting random effects of the three-compartment model to clearance and central volume of distribution. Two blood samples, one early and one 300 min post injection, were sufficient to estimate iohexol clearance. A simplified three-compartment model is optimal to estimate iohexol clearance in elderly patients with reduced GFR.
format	article
author	Max Taubert Elke Schaeffner Peter Martus Markus van der Giet Uwe Fuhr Amina Lösment Natalie Ebert
author_facet	Max Taubert Elke Schaeffner Peter Martus Markus van der Giet Uwe Fuhr Amina Lösment Natalie Ebert
author_sort	Max Taubert
title	Advancement of pharmacokinetic models of iohexol in patients aged 70 years or older with impaired kidney function
title_short	Advancement of pharmacokinetic models of iohexol in patients aged 70 years or older with impaired kidney function
title_full	Advancement of pharmacokinetic models of iohexol in patients aged 70 years or older with impaired kidney function
title_fullStr	Advancement of pharmacokinetic models of iohexol in patients aged 70 years or older with impaired kidney function
title_full_unstemmed	Advancement of pharmacokinetic models of iohexol in patients aged 70 years or older with impaired kidney function
title_sort	advancement of pharmacokinetic models of iohexol in patients aged 70 years or older with impaired kidney function
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/f6a1f16dee5843c097c784d47edb7de6
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Advancement of pharmacokinetic models of iohexol in patients aged 70 years or older with impaired kidney function

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