Universität zu Köln

Taubert, Max, Schaeffner, Elke, Martus, Peter, van der Giet, Markus ORCID: 0000-0003-3590-5451, Fuhr, Uwe, Loesment, Amina and Ebert, Natalie (2021). Advancement of pharmacokinetic models of iohexol in patients aged 70 years or older with impaired kidney function. Sci Rep, 11 (1). BERLIN: NATURE PORTFOLIO. ISSN 2045-2322

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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 mu g/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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Taubert, Max UNSPECIFIED UNSPECIFIED UNSPECIFIED Schaeffner, Elke UNSPECIFIED UNSPECIFIED UNSPECIFIED Martus, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED van der Giet, Markus UNSPECIFIED orcid.org/0000-0003-3590-5451 UNSPECIFIED Fuhr, Uwe UNSPECIFIED UNSPECIFIED UNSPECIFIED Loesment, Amina UNSPECIFIED UNSPECIFIED UNSPECIFIED Ebert, Natalie UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-590348
DOI:	10.1038/s41598-021-01892-1
Journal or Publication Title:	Sci Rep
Volume:	11
Number:	1
Date:	2021
Publisher:	NATURE PORTFOLIO
Place of Publication:	BERLIN
ISSN:	2045-2322
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GLOMERULAR-FILTRATION-RATE; PLASMA-CLEARANCE; GFR; DISAPPEARANCE; DISEASE Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/59034