Universität zu Köln

Taubert, Max ORCID: 0000-0001-8925-7782, Ebert, Natalie, Martus, Peter, van der Giet, Markus ORCID: 0000-0003-3590-5451, Fuhr, Uwe and Schaeffner, Elke (2018). Using a three-compartment model improves the estimation of iohexol clearance to assess glomerular filtration rate. Sci Rep, 8. LONDON: NATURE PUBLISHING GROUP. ISSN 2045-2322

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Abstract

Plasma clearance of iohexol is a key tool to precisely determine glomerular filtration rate (GFR) in clinical research and clinical practice. Despite evidence that iohexol pharmacokinetics are described best by three-compartment models, two-compartment approaches (Schwartz approach) are customary, which might result in avoidable bias and imprecision. We aimed to provide a population pharmacokinetic (popPK) model of iohexol by re-evaluating data from the Berlin Initiative Study (BIS) to compare respective clearance estimates to the Schwartz approach and to assess the impact of revised clearance estimates on the BIS equations. A popPK model was developed based on iohexol plasma samples (8-10 per subject, iohexol dose 3235 mg) from 570 elderly patients. A three-compartment model appropriately described the pharmacokinetics of iohexol (clearance 57.4 mL/min, CV 33%). Compared to the three-compartment model, clearance values were overestimated by the Schwartz approach (bias 6.5 mL/min), resulting in limited effects on regression coefficients of the BIS equations (e.g., proportionality factor of B152 changed from 767 to 720). Predictions based on the B152 equation were biased (5.4 mL/min/1.73 m(2)) and the sensitivity to detect a GFR < 60 mL/min/1.73 m(2) was low compared to the revised equation (72% versus 89%). Three-compartment models should be employed to assess iohexol pharmacokinetics.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Taubert, Max UNSPECIFIED orcid.org/0000-0001-8925-7782 UNSPECIFIED Ebert, Natalie 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 Schaeffner, Elke UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-162366
DOI:	10.1038/s41598-018-35989-x
Journal or Publication Title:	Sci Rep
Volume:	8
Date:	2018
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	2045-2322
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CHRONIC KIDNEY-DISEASE; PLASMA-CLEARANCE; PHARMACOKINETICS Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/16236