Universität zu Köln

Chen, Zhendong ORCID: 0000-0002-2035-635X, Dong, Qian ORCID: 0000-0001-7201-7643, Dokos, Charalambos ORCID: 0000-0002-7883-2558, Boland, Jana ORCID: 0009-0006-4660-5816, Fuhr, Uwe ORCID: 0000-0001-7087-5871 and Taubert, Max ORCID: 0000-0001-8925-7782 (2025). A Joint Pharmacometric Model of Iohexol and Creatinine Administered through a Meat Meal to Assess GFR and Renal OCT2/MATE Activity. Clinical Pharmacology & Therapeutics, 118 (2). pp. 510-519. Wiley. ISSN 0009-9236

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Abstract

Accurately assessing glomerular filtration rate (GFR) from plasma creatinine concentrations is challenging in patients with unstable renal function. This study aimed to refine the understanding of creatinine kinetics for more reliable assessments of GFR and net creatinine tubular secretion (nCTS) via OCT2/MATE in humans. In a clinical study of 14 healthy volunteers, iohexol was administered intravenously as a reference GFR marker, and creatinine was introduced through a meat meal. A joint pharmacometric model was developed using dense plasma and urine sampling. Simulations were used to evaluate the effect of different creatinine volume of distribution (V d ) values on GFR estimation after acute kidney injury (AKI) and to assess the impact of limited sampling strategies on GFR and nCTS estimation. Pharmacokinetic parameters for iohexol and creatinine aligned with reported values, but a lower V d of 41% of total body weight and a nCTS fraction of 31% relative to overall creatinine clearance were observed. Commonly used equations based on single‐point creatinine measurement all overestimated GFR, with the Modification of Diet in Renal Disease (MDRD) equation performing best, followed by Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) 2009 equation. Simulations demonstrate the effect of V d estimate accuracy on detecting AKI from creatinine plasma concentrations only. Following low‐dose iohexol administration, a single plasma sample at 5 hours and a urine sample from 0 to 5 hours provided accurate estimates of both GFR and nCTS using the joint model and enabled adequate correction for incomplete urine collection. This approach shows promise for assessing renal transporter activity based on estimated nCTS.

Item Type:	Article
Creators:	Creators Email ORCID ORCID Put Code Chen, Zhendong UNSPECIFIED https://orcid.org/0000-0002-2035-635X UNSPECIFIED Dong, Qian UNSPECIFIED https://orcid.org/0000-0001-7201-7643 UNSPECIFIED Dokos, Charalambos UNSPECIFIED https://orcid.org/0000-0002-7883-2558 UNSPECIFIED Boland, Jana UNSPECIFIED https://orcid.org/0009-0006-4660-5816 UNSPECIFIED Fuhr, Uwe UNSPECIFIED https://orcid.org/0000-0001-7087-5871 UNSPECIFIED Taubert, Max UNSPECIFIED https://orcid.org/0000-0001-8925-7782 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-794533
Identification Number:	10.1002/cpt.3612
Journal or Publication Title:	Clinical Pharmacology & Therapeutics
Volume:	118
Number:	2
Page Range:	pp. 510-519
Number of Pages:	10
Date:	25 August 2025
Publisher:	Wiley
ISSN:	0009-9236
Language:	English
Faculty:	Faculty of Medicine
Divisions:	Faculty of Medicine > Pharmakologie > Instítut für Pharmakologie
Subjects:	Medical sciences Medicine
['eprint_fieldname_oa_funders' not defined]:	Publikationsfonds UzK
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/79453