title: 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.
authors.affiliation: Ospedale Regionale Microcitemie, Dipartimento di Scienze, Biomediche e Biotechnologie, Università di Cagliari, Italy.
authors.forename: Renzo
authors.initials: R
authors.lastname: Galanello
authors.forename: Antonio
authors.initials: A
authors.lastname: Piga
authors.forename: Maria Domenica
authors.initials: MD
authors.lastname: Cappellini
authors.forename: Gian Luca
authors.initials: GL
authors.lastname: Forni
authors.forename: Antonella
authors.initials: A
authors.lastname: Zappu
authors.forename: Raffaella
authors.initials: R
authors.lastname: Origa
authors.forename: Catherine
authors.initials: C
authors.lastname: Dutreix
authors.forename: Rossella
authors.initials: R
authors.lastname: Belleli
authors.forename: John M
authors.initials: JM
authors.lastname: Ford
authors.forename: Gilles-Jacques
authors.initials: GJ
authors.lastname: Rivière
authors.forename: Sébastien
authors.initials: S
authors.lastname: Balez
authors.forename: Daniele
authors.initials: D
authors.lastname: Alberti
authors.forename: Romain
authors.initials: R
authors.lastname: Séchaud
mesh_terms: 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*
chemical_list: D001565:Benzoates; D007502:Iron Chelating Agents; D014230:Triazoles; D000077588:Deferasirox