title: Reduction in labile plasma iron during treatment with deferasirox, a once-daily oral iron chelator, in heavily iron-overloaded patients with beta-thalassaemia.
abstract: This subgroup analysis evaluated the effect of once-daily oral deferasirox on labile plasma iron (LPI) levels in patients from the prospective, 1-yr, multicentre ESCALATOR study. Mean baseline liver iron concentration and median serum ferritin levels were 28.6 +/- 10.3 mg Fe/g dry weight and 6334 ng/mL respectively, indicating high iron burden despite prior chelation therapy. Baseline LPI levels (0.98 +/- 0.82 micromol/L) decreased significantly to 0.12 +/- 0.16 micromol/L, 2 h after first deferasirox dose (P = 0.0006). Reductions from pre- to post-deferasirox administration were also observed at all other time points. Compared to baseline, there was a significant reduction in preadministration LPI that reached the normal range at week 4 and throughout the remainder of the study (P < or = 0.02). Pharmacokinetic analysis demonstrated an inverse relationship between preadministration LPI levels and trough deferasirox plasma concentrations. Once-daily dosing with deferasirox > or =20 mg/kg/d provided sustained reduction in LPI levels in these heavily iron-overloaded patients, suggesting 24-h protection from LPI. Deferasirox may therefore reduce unregulated tissue iron loading and prevent further end-organ damage.
authors.affiliation: Department of Hematology, College of Medicine, Sultan Qaboos University, Muscat, Oman. asdoc@omantel.net.om
authors.forename: Shahina
authors.initials: S
authors.lastname: Daar
authors.forename: Anil
authors.initials: A
authors.lastname: Pathare
authors.forename: Hanspeter
authors.initials: H
authors.lastname: Nick
authors.forename: Ulrike
authors.initials: U
authors.lastname: Kriemler-Krahn
authors.forename: Abdel
authors.initials: A
authors.lastname: Hmissi
authors.forename: Dany
authors.initials: D
authors.lastname: Habr
authors.forename: Ali
authors.initials: A
authors.lastname: Taher
mesh_terms: D000293:Adolescent; D000328:Adult; D001565:Benzoates / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002648:Child; D000077588:Deferasirox; D005260:Female; D005293:Ferritins / Q000097:blood; D006801:Humans; D007501:Iron / Q000032:analysis / Q000097:blood*; D007502:Iron Chelating Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019190:Iron Overload / Q000188:drug therapy*; D008099:Liver / Q000737:chemistry; D008297:Male; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage* / Q000493:pharmacokinetics; D055815:Young Adult; D017086:beta-Thalassemia / Q000188:drug therapy*
chemical_list: D001565:Benzoates; D007502:Iron Chelating Agents; D014230:Triazoles; D005293:Ferritins; D007501:Iron; D000077588:Deferasirox