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

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 non-kidney clearance being predominant. Due to their limited therapeutic window, many TKI display considerable intra- 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 acute kidney injury (AKI) and chronic kidney disease (CKD), among cancer patients is explored in terms of their impact on TKI pharmacokinetics. Lastly, the potential nephrotoxicity associated with TKI is also examined.

Keywords

Tyrosine Kinase inhibitors pharmacokinetics drug-drug interactions cytochromes transporters kidney diseases metabolism Tyrosine Kinase inhibitors pharmacokinetics drug-drug interactions cytochromes transporters kidney diseases metabolism

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Life Sciences [q-bio]

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PKPD.TKI.CJASN.subimission revised version 5_clean.pdf (631.45 Ko)

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https://hal.u-pec.fr/hal-04347296

Submitted on : Friday, December 15, 2023-3:38:49 PM

Last modification on : Sunday, April 7, 2024-3:20:32 AM

Dates and versions

hal-04347296 , version 1 (15-12-2023)

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HAL Id : hal-04347296 , version 1
DOI : 10.2215/CJN.0000000000000395

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Anne Hulin, Thibaut Gelé, Charlotte Fenioux, Emmanuelle Kempf, Dil Sahali, et al.. Pharmacology of Tyrosine Kinase Inhibitors: Implications for Patients with Kidney Diseases. Clinical Journal of the American Society of Nephrology, 2023, ⟨10.2215/CJN.0000000000000395⟩. ⟨hal-04347296⟩

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