Title

 

Authors

S. De Francia¹, D. Massano², E. Pirro¹, F. Piccione¹, M. Serra², F. Di Carlo¹, A. Piga².
 
¹Clinical Pharmacology of San Luigi Hospital, University of Turin;
²Thalassemia Centerof San Luigi Hospital, University of Turin.

 

Abstract

 
Deferasirox (DFX) is a once-daily oral iron chelator developed for the treatment of iron overload. The metabolization rate is variable and seems to play a key role in the inconstant efficacy rate observed in most of the studies. DFX plasma concentration measurement could be useful to calibrate individual drug dosing to optimize iron chelation efficacy. The aim of the present study has been to explore the possibility to perform routinely DFX measurement and its potential association with efficacy of chelation. We enrolled thalassemia major patients that were taking DFX at least from six months with a compliance >70%. Blood drawing was done at 24±1 hours from the last drug administration and sample was hold at 4°C till centrifugation was performed. DFX plasma concentration was measured, after specific drug extraction, by High Pressure Liquid Chromatography with Ultraviolet detection. To define DFX response, iron overload parameters (serum ferritin and liver iron concentration by SQUID) were obtained from follow-up of each patient. In 4 months we collected 65 samples from 50 patients on daily iron chelation by DFX (median dose 29 mg/Kg/day). Median drug level achieved was 32μmol/l after 24±1 hours from the last drug administration. Thirtyseven patients (16 women, 21 men) had inclusion criteria for the study. Mean age at blood sampling was 32 ±11 years and median DFX dose administrated was 30 mg/kg/day. The median DFX concentration was 32μmol/l with a difference according to sex: 60μmol/l for women and 19μmol/l for men. As a whole DFX levels did not correlate with the dose assumed. We found a negative relationship between DFX plasma levels and iron overload parameters. Patients with poor response according to Chirnomas [1] had a lower DFX concentration (median 10μmol/l) than good responders (median 44μmol/l). Our protocol to measure DFX concentration can fit with the clinical routine of thalassemic patients and it seems easy to be introduced in the daily routine as non invasive practice. There is an association with DFX concentration and treatment efficacy: monitoring circulating DFX levels, then, could help to optimize the individual dose of DFX to maximize the efficacy.
 
[1] D. Chirnomas et al. Blood. 114, 4009 (2009).