title: Pharmacokinetics and safety of deferasirox in subjects with chronic kidney disease undergoing haemodialysis.
abstract: OBJECTIVE
  Treatment of chronic kidney disease (CKD) includes parenteral iron therapy, and these infusions can lead to iron overload. Secondary iron overload is typically treated with iron chelators, of which deferasirox is one of the most promising. However, it has not been studied in patients with CKD and iron overload.
  
  
  METHODS
  A pilot study was conducted to evaluate the pharmacokinetics and safety of deferasirox in eight haemodialysis-dependent patients, who were receiving intravenous iron for treatment of anaemia of CKD. Deferasirox was administered at two doses (10 mg/kg and 15 mg/kg), either acute (once daily for 2 days) or steady-state (once daily for 2 weeks).
  
  
  RESULTS
  A dose of 10 mg/kg in either protocol was not sufficient to achieve a plasma concentration in the therapeutic range (acute peak 14.1 and steady-state 22.8 μmol/L), while 15 mg/kg in either protocol maintained plasma concentration well above this range (acute peak 216 and steady-state 171 μmol/L). Plasma concentration observed at 15 mg/kg was well above that expected for this dose (40-50 μmol/L), although no adverse clinical events were observed.
  
  
  CONCLUSIONS
  This study highlights the need to profile drugs such as deferasirox in specific patient groups, such as those with CKD and iron overload.
authors: School of Veterinary and Life Sciences, Murdoch University, Australia. g.maker@murdoch.edu.au
authors: Garth L
authors: GL
authors: Maker
authors: Brian
authors: B
authors: Siva
authors: Kevin T
authors: KT
authors: Batty
authors: Robert D
authors: RD
authors: Trengove
authors: Paolo
authors: P
authors: Ferrari
authors: John K
authors: JK
authors: Olynyk
mesh_terms: D000368:Aged; D018798:Anemia, Iron-Deficiency / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D019540:Area Under Curve; D001565:Benzoates / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D002853:Chromatography, Liquid; D000077588:Deferasirox; D004334:Drug Administration Schedule; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006397:Hematinics / Q000009:adverse effects*; D006801:Humans; D007502:Iron Chelating Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D019190:Iron Overload / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D006435:Renal Dialysis / Q000009:adverse effects; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000150:complications / Q000628:therapy*; D053719:Tandem Mass Spectrometry; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D014904:Western Australia
chemical_list: D001565:Benzoates; D006397:Hematinics; D007502:Iron Chelating Agents; D014230:Triazoles; D000077588:Deferasirox