Pharmacokinetics and safety of deferasirox in subjects with chronic kidney disease undergoing haemodialysis

AIM: 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...

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Main Authors: Maker, G., Siva, B., Batty, Kevin, Trengove, R., Ferrari, P., Olynyk, John
Format: Journal Article
Published: Wiley-Blackwell Publishing Asia 2013
Subjects:
Online Access:http://hdl.handle.net/20.500.11937/11024
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author Maker, G.
Siva, B.
Batty, Kevin
Trengove, R.
Ferrari, P.
Olynyk, John
author_facet Maker, G.
Siva, B.
Batty, Kevin
Trengove, R.
Ferrari, P.
Olynyk, John
author_sort Maker, G.
building Curtin Institutional Repository
collection Online Access
description AIM: 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 mmol/L), while 15 mg/kg in either protocol maintained plasma concentration well above this range (acute peak 216 and steady-state 171 mmol/L). Plasma concentration observed at 15 mg/kg was well above that expected for this dose (40–50 mmol/L), although no adverse clinical events were observed.CONCLUSION: This study highlights the need to profile drugs such as deferasirox in specific patient groups, such as those with CKD and iron overload.
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spelling curtin-20.500.11937-110242017-09-13T15:54:44Z Pharmacokinetics and safety of deferasirox in subjects with chronic kidney disease undergoing haemodialysis Maker, G. Siva, B. Batty, Kevin Trengove, R. Ferrari, P. Olynyk, John ferritin deferasirox iron overload chelation chronic kidney disease AIM: 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 mmol/L), while 15 mg/kg in either protocol maintained plasma concentration well above this range (acute peak 216 and steady-state 171 mmol/L). Plasma concentration observed at 15 mg/kg was well above that expected for this dose (40–50 mmol/L), although no adverse clinical events were observed.CONCLUSION: This study highlights the need to profile drugs such as deferasirox in specific patient groups, such as those with CKD and iron overload. 2013 Journal Article http://hdl.handle.net/20.500.11937/11024 10.1111/nep.12035 Wiley-Blackwell Publishing Asia fulltext
spellingShingle ferritin
deferasirox
iron overload
chelation
chronic kidney disease
Maker, G.
Siva, B.
Batty, Kevin
Trengove, R.
Ferrari, P.
Olynyk, John
Pharmacokinetics and safety of deferasirox in subjects with chronic kidney disease undergoing haemodialysis
title Pharmacokinetics and safety of deferasirox in subjects with chronic kidney disease undergoing haemodialysis
title_full Pharmacokinetics and safety of deferasirox in subjects with chronic kidney disease undergoing haemodialysis
title_fullStr Pharmacokinetics and safety of deferasirox in subjects with chronic kidney disease undergoing haemodialysis
title_full_unstemmed Pharmacokinetics and safety of deferasirox in subjects with chronic kidney disease undergoing haemodialysis
title_short Pharmacokinetics and safety of deferasirox in subjects with chronic kidney disease undergoing haemodialysis
title_sort pharmacokinetics and safety of deferasirox in subjects with chronic kidney disease undergoing haemodialysis
topic ferritin
deferasirox
iron overload
chelation
chronic kidney disease
url http://hdl.handle.net/20.500.11937/11024