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Current Drug Metabolism

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ISSN (Print): 1389-2002
ISSN (Online): 1875-5453

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Research Article

Effect of Aging on Deferasirox Therapy in Transfusion-dependent Patients. A Prospective- Retrospective, Cohort-study

Author(s): Valeria Marini, Valeria Maria Pinto, Manuela Stella, Carmen Fucile, Francesca Lantieri, Giacomo Luci, Barbara Gianesin, Lorenzo Bacigalupo, Gian Luca Forni and Francesca Mattioli*

Volume 23, Issue 13, 2022

Published on: 26 December, 2022

Page: [1072 - 1079] Pages: 8

DOI: 10.2174/1389200224666221209144420

open access plus

Abstract

Background: Iron-chelation therapy is life-saving in patients on a chronic transfusion regimen as it reduces organ damage related to iron deposition in the tissues. Deferasirox, an iron-chelator, is characterized by pharmacokinetics variability, and some patients may discontinue the treatment due to toxicities.

Objective: Understanding whether deferasirox plasma levels are related to patients' specific characteristics could help to optimize DFX dosage.

Methods: We analyzed deferasirox plasma concentration in 57 transfusion-dependent anemic patients using the HPLC method in this prospective-retrospective cohort study. All outpatients (3 to 98 years) were treated with deferasirox (film-coated tablet) for at least one year (median dose, 16.5 mg/Kg once a day). Deferasirox plasma concentration was normalized for dose/Kg (C/dose) and corrected with a linear regression model that relates C/dose and the time of blood sampling (Cref/dose).

Results: No significant differences in Cref/dose were found between males and females, either between different types of hemoglobinopathies or depending on the presence of the UGT1A1*28 polymorphism. Cref/dose has a positive and significant correlation with age, creatinine, and direct bilirubin. Cref/dose, instead, has a negative and significant correlation with Liver Iron Concentration (LIC), ferritin, and eGFR. Cref/dose was significantly different between three age categories <18yrs, 18-50yrs, and >50yrs, with Cref/dose median values of 1.0, 1.2, and 1.5, respectively.

Conclusion: The study evidenced that to ensure the efficacy of deferasirox in terms of control over LIC and, at the same time, a lesser influence on renal function, the dose of the drug to be administered to an elderly patient could be reduced.

Keywords: Iron chelation, deferasirox, transfusion-dependent patients, physiologically-based pharmacokinetics, tolerability, aging, therapeutic drug monitoring.

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