Effect of food, type of food, and time of food intake on deferasirox bioavailability: recommendations for an optimal deferasirox administration regimen.
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.
Galanello
Renzo
R
Ospedale Regionale Microcitemie, Dipartimento di Scienze, Biomediche e Biotechnologie, Università di Cagliari, Italy.
Piga
Antonio
A
Cappellini
Maria Domenica
MD
Forni
Gian Luca
GL
Zappu
Antonella
A
Origa
Raffaella
R
Dutreix
Catherine
C
Belleli
Rossella
R
Ford
John M
JM
Rivière
Gilles-Jacques
GJ
Balez
Sébastien
S
Alberti
Daniele
D
Séchaud
Romain
R
D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D001565:Benzoates / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D000077588:Deferasirox; D004435:Eating / Q000502:physiology*; D005260:Female; D005502:Food; D018565:Food-Drug Interactions; D006801:Humans; D007408:Intestinal Absorption; D007502:Iron Chelating Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019190:Iron Overload / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D013056:Spectrophotometry, Ultraviolet; D014230:Triazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*
D001565:Benzoates; D007502:Iron Chelating Agents; D014230:Triazoles; D000077588:Deferasirox