title: Deferasirox-Iron Complex Formation Ratio as an Indicator of Long-term Chelation Efficacy in β-Thalassemia Major.
abstract: β-Thalassemia major patients with higher total drug levels [deferasirox (DEFR) plus its iron complex] do not yield better serum ferritin (SF) control. This study aimed to determine the concentrations of DEFR and its iron complex (Fe-[DEFR]2) in thalassemia patients to predict the chelation efficacy in terms of SF and cardiac T2* values.
  
  
  
  Patients' steady-state drug levels at trough (Ctrough) and 2 hours postdose (C2h) were determined. Because iron deposition may cause changes in the hepatic metabolism of amino acids, the concentrations of 40 amino acids in plasma were also assayed at 2 hours postdose.
  
  
  
  A total of 28 patients either dosing daily or twice daily were recruited. After a 1-month DEFR maintenance therapy, 38.8% and 30% of patients from groups of once-daily and twice-daily, respectively, had a plasma DEFR-iron complex formation ratio higher than 0.05 [High Chelation Ratio, (HCR)]. After a 6-month follow-up, those patients who had a HCR (n = 10) at C2h showed more favorable median changes in SF and cardiac T2* values (-388.0, +10.1) than those with a low DEFR-iron complex formation ratio (Low Chelation Ratio; n = 18; +10.5; +4.5) compared with the baseline. The levels of plasma L-arginine, L-alanine, L-glycine, L-norleucine, and L-serine were significantly lower in patients with the low Chelation Ratio condition than the levels in HCR patients.
  
  
  
  This therapeutic drug monitoring study revealed that a DEFR-iron complex formation ratio at C2h might be an applicable indicator of the efficacy of long-term DEFR iron chelation therapy. A better iron-control response to DEFR was observed in the patients with HCRs. The trends for the ratio might have value in dose-setting and need to be validated in a larger cohort.
authors.affiliation: *Division of Haematology/Oncology, Department of Paediatrics, National Taiwan University Hospital; and †Department of Clinical Pharmacy, School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan.
authors.forename: Meng-Yao
authors.initials: MY
authors.lastname: Lu
authors.forename: Ting-Hao
authors.initials: TH
authors.lastname: Lin
authors.forename: Po-Hung
authors.initials: PH
authors.lastname: Chiang
authors.forename: Pei-Hsin
authors.initials: PH
authors.lastname: Kuo
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.forename: Wen-Hsin
authors.initials: WH
authors.lastname: Wu
authors.forename: Kai-Hsin
authors.initials: KH
authors.lastname: Lin
authors.forename: Tzu-Hua
authors.initials: TH
authors.lastname: Wu
mesh_terms: D000293:Adolescent; D000328:Adult; D000596:Amino Acids / Q000097:blood; D001565:Benzoates / Q000008:administration & dosage* / Q000097:blood* / Q000493:pharmacokinetics; D000077588:Deferasirox; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006801:Humans; D007501:Iron / Q000097:blood*; D007502:Iron Chelating Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008099:Liver / Q000378:metabolism; D008297:Male; D014230:Triazoles / Q000008:administration & dosage* / Q000097:blood* / Q000493:pharmacokinetics; D055815:Young Adult; D017086:beta-Thalassemia / Q000097:blood* / Q000188:drug therapy*
chemical_list: D000596:Amino Acids; D001565:Benzoates; D007502:Iron Chelating Agents; D014230:Triazoles; D007501:Iron; D000077588:Deferasirox