Pharmacology of Tyrosine Kinase Inhibitors: Implications for Patients with Kidney Diseases

Anne Hulin; Thibaut Gelé; Charlotte Fenioux; Emmanuelle Kempf; Dil Sahali; Christophe Tournigand; Mario Ollero

doi:10.2215/CJN.0000000000000395

Pharmacology of Tyrosine Kinase Inhibitors: Implications for Patients with Kidney Diseases

Clin J Am Soc Nephrol. 2023 Dec 11. doi: 10.2215/CJN.0000000000000395. Online ahead of print.

Authors

Anne Hulin^{1

2}, Thibaut Gelé^{1

2}, Charlotte Fenioux³, Emmanuelle Kempf^{2

3}, Dil Sahali^{2

4}, Christophe Tournigand^{2

3}, Mario Ollero²

Affiliations

¹ Pharmacology Laboratory, University Medicine Department of Biology-Pathology, AP-HP, GH Henri Mondor, University Paris-Est Creteil, Créteil, France.
² University Paris Est Creteil, INSERM, IMRB, F-94010 Creteil, France.
³ Oncology Unit, University Medicine Department of Cancer, AP-HP, GH Henri Mondor, University Paris-Est Creteil, Créteil, France.
⁴ Nephrology Unit, University Medicine Department of Medicine, AP-HP, GH Henri Mondor, University Paris-Est Creteil, Créteil, France.

PMID: 38079278
DOI: 10.2215/CJN.0000000000000395

Abstract

Tyrosine kinase inhibitors (TKI) have introduced a significant advancement in cancer management. These compounds are administered orally, and their absorption holds a pivotal role in determining their variable efficacy. They exhibit extensive distribution within the body, binding strongly to both plasma and tissue proteins. Often reliant on efflux and influx transporters, TKI undergo primary metabolism by intestinal and hepatic cytochrome P450 enzymes, with nonkidney clearance being predominant. Owing to their limited therapeutic window, many TKI display considerable intraindividual and interindividual variability. This review offers a comprehensive analysis of the clinical pharmacokinetics of TKI, detailing their interactions with drug transporters and metabolic enzymes, while discussing potential clinical implications. The prevalence of kidney conditions, such as AKI and CKD, among patients with cancer is explored in their effect on TKI pharmacokinetics. Finally, the potential nephrotoxicity associated with TKI is also examined.