Universität zu Köln

Dong, Qian ORCID: 0000-0001-7201-7643 (2025). Assessment of individual pharmacokinetic processes in renal drug elimination. PhD thesis, Universität zu Köln.

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Abstract

Renal elimination is a major route of drug clearance, influencing exposure and therapeutic outcomes, especially in patients with impaired kidney function. This cumulative dissertation aims to improve the evaluation of renal drug elimination by optimizing iohexol-based methods for measuring glomerular filtration rate (GFR) and examining the role of kidney transporters. Three complementary studies were conducted. The first evaluated simplified methods to estimate iohexol clearance from blood samples. Using correction formulas in one- and two-compartment pharmacokinetic (PK) models, reliable GFR estimates were achieved. Both approaches showed acceptable performance, offering practical alternatives to complex models in clinical settings. The second study assessed the PK and transporter involvement of a reduced iohexol dose (259 mg). Results confirmed iohexol is cleared solely by glomerular filtration, with no significant transporter interaction. Its predictable and dose-proportional PK support its use as a safe and reliable GFR marker, even in patients with kidney impairment. The third study used population PK modeling to explore adefovir disposition, a substrate of the renal organic anion transporter (OAT) 1, within a transporter probe cocktail. Co-administration slightly increased adefovir exposure, likely due to altered absorption rather than transporter interaction. Renal clearance (CLR) was unaffected, and no saturation of OAT1-mediated elimination was observed. Adefovir CLR is thus a suitable marker of OAT1 activity. Together, these studies offer practical tools and insights for assessing kidney function and transporter-related drug clearance, supporting more individualized and efficient clinical decision-making.

Item Type:	Thesis (PhD thesis)
Creators:	Creators Email ORCID ORCID Put Code Dong, Qian qian.dong@uk-koeln.de orcid.org/0000-0001-7201-7643 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-785844
Date:	2025
Language:	English
Faculty:	Faculty of Medicine
Divisions:	Faculty of Medicine > Pharmakologie > Instítut für Pharmakologie
Subjects:	Natural sciences and mathematics Medical sciences Medicine
Uncontrolled Keywords:	Keywords Language Renal elimination English Glomerular filtration rate English Transporter-mediated drug-drug interaction English
Date of oral exam:	2 July 2025
Referee:	Name Academic Title Kurschat, Christine Prof. Dr. Hellmich, Martin Prof. Dr.
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/78584