Effect of Food, Type of Food, and Time of Food Intake on Deferasirox Bioavailability: Recommendations for an Optimal Deferasirox Administration Regimen

Abstract

Deferasirox (ICL670) is representative of a new class of tridentate iron chelators, formulated as tablets for dispersion. Deferasirox has exhibited high potency and a clinically manageable safety profile in preclinical models and in an extensive clinical program. The effect of food and time of food intake on the pharmacokinetics of deferasirox was investigated in healthy volunteers and patients with transfusional hemosiderosis. The bioequivalence of a single oral dose of deferasirox (20 mg/kg) was assessed following administration either before a high-fat or standard breakfast or concurrent with a standard breakfast in comparison with fasted conditions in healthy volunteers. The bioavailability of deferasirox was determined following a single oral dose (20 mg/kg) under fed and fasted conditions in patients. These data show that the type of food, caloric content, and fat content of the meal influence the bioavailability of deferasirox when consumed concomitantly. In contrast, this is not the case when deferasirox is administered at least 30 minutes before a meal. In conclusion, it is recommended that deferasirox be administered at least 30 minutes prior to meals. When this is not feasible, deferasirox should be administered consistently at the same time before meals to limit the sources of variability that affect absorption.

A new HPLC UV validated method for therapeutic monitoring of deferasirox in thalassaemic patients

“…The absence of correlation between DFX plasma Ctrough and dose, as shown in Fig. 4, substantiates the prediction of an high inter individual variability in pK, as shown by recent phase II studies observations [8], [15] and [26]. The negative correlation, instead, observed between DFX plasma Ctrough and patients ferritin concentrations (Fig.…”

“…The LOQ (0.15625 μg/ml) of the developed assay makes methodology suitable to perform DFX therapeutic monitoring in thalassaemic treated patients. DFX values obtained from plasma of patients resulted in the expected range of concentrations according to available literature data [8], [15] and [26]. As shown in Fig.…”

“…Range within that testing method linearity was from 0.078125 to 40 μg/ml of DFX, according phase II DFX studies data [8], [15] and [26]. Calibration curves, over the concentrations range chosen, were built with the spike height ratios of each STD and IS, and fitted using linear regression.…”

Toward optimizing the use of deferasirox: potential benefits of combined use with deferoxamine

“…haematologica | 2013; 98(1) food on drug absorption, 44 ineffective erythropoiesis, splenectomy 45 and overall iron burden, contribute to such variability. In 2008, Cohen et al showed that the rate of transfusion correlates with the effectiveness of DFX and DFO.…”

Iron Chelation Therapy in Thalassemia Syndromes

“…For this reason the drug must be taken at least 30 minute before eating, preferably at the same time every day. 41 The patient age is another parameter influencing the bioavailability which is lower for the adolescents (12-17 years old) and children (2-12 years old).…”