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:
CreatorsEmailORCIDORCID Put Code
Taubert, MaxUNSPECIFIEDorcid.org/0000-0001-8925-7782UNSPECIFIED
Ebert, NatalieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Martus, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van der Giet, MarkusUNSPECIFIEDorcid.org/0000-0003-3590-5451UNSPECIFIED
Fuhr, UweUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schaeffner, ElkeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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:
KeywordsLanguage
CHRONIC KIDNEY-DISEASE; PLASMA-CLEARANCE; PHARMACOKINETICSMultiple languages
Multidisciplinary SciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/16236

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