Determination of deferasirox plasma concentrations: do gender, physical and genetic differences affect chelation efficacy?

Mattioli, Francesca; Puntoni, Matteo; Marini, Valéria; Fucile, Carmen; Milano, Giulia; Robbiano, Luigi; Perrotta, Silverio; Pinto, Valeria; Martelli, Antonietta; Forni, Gian Luca

doi:10.1111/ejh.12419

Cited by 18 publications

(14 citation statements)

References 22 publications

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“…Measurement, by high performance liquid chromatography (HPLC) assay, previously described and validated, 12 , 13 of DFX plasma concentration confirmed a moderate increase of the drug plasmatic level (C trough =27 µM; normal C trough value <20 µM; C DFX /D DFX ratio =0.56). Tacrolimus therapeutic plasma concentrations were maintained at about 10 ng/mL.…”

Section: Case Reportsmentioning

confidence: 71%

What is known about deferasirox chelation therapy in pediatric HSCT recipients: two case reports of metabolic acidosis

Fucile¹,

Mattioli²,

Marini³

et al. 2018

TCRM

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To date, in pediatric field, various hematological malignancies are increasingly treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Iron overload and systemic siderosis often occur in this particular cohort of patients and are associated with poor prognosis. We describe herein the case of two allo-HSCT patients, on treatment with deferasirox; they showed histopathological elements compatible with venoocclusive disease or vanishing bile duct syndrome in ductopenic evolution before deferasirox started. The first patient developed drug-induced liver damage with metabolic acidosis and the second one a liver impairment with Fanconi syndrome. After withdrawing deferasirox treatment, both patients showed improvement. Measurements of drug plasma concentrations were performed by HPLC assay. The reduction and consequent disappearance of symptoms after the suspension of deferasirox substantiate its role in inducing hepatic damage, probably enabling the diagnosis of drug-induced liver damage. But the difficulties in diagnosing drug-related toxicity must be underlined, especially in compromised subjects. For these reasons, in patients requiring iron-chelating therapy, close and careful drug therapeutic monitoring is strongly recommended.

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Section: Case Reportsmentioning

confidence: 71%

What is known about deferasirox chelation therapy in pediatric HSCT recipients: two case reports of metabolic acidosis

Fucile¹,

Mattioli²,

Marini³

et al. 2018

TCRM

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“…DFX glucuronidation is controlled by the UDP-glucuronosyltransferase 1A subfamily (UGT1A1 and, to a lesser extent, UGT1A3). UGT1A1 polymorphism has been recognized as an important element in drug tolerance because it increases the risk of toxicity of drugs metabolized via glucuronidation [ 11 ].…”

Section: Discussionmentioning

confidence: 99%

“…Deferasirox plasma concentrations (C-DFX) were determined by high performance liquid chromatography (HPLC) assay, as previously described and validated [ 10 , 11 ]. Plasma samples were processed by liquid–liquid extraction using methanol.…”

Section: Methodsmentioning

confidence: 99%

Safety and tolerability of deferasirox in pediatric hematopoietic stem cell transplant recipients: one facility's five years’ experience of chelation treatment

et al. 2017

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42 pediatric patients with iron overload, who underwent liver biopsy and DFX treatment after hematopoietic stem cell transplantation were included in the study group. The patients were divided into two groups diversified according to deferasirox trough plasma concentrations (DFX Ctrough) with cut-off equal to10 mcg/mL. The average dose of DFX was 25.9 mg/kg in the DFX Ctrough < 10 mcg/mL group versus 19.2 mg/kg in the DFX Ctrough > 10 mcg/mL group (p=0,0003). The mean duration of DFX treatment was 135.7 days in the DFX Ctrough < 10 mcg/mL group versus 41.8 days in the DFX Ctrough > 10 mcg/mL group (p<0.0001). The mean tissue iron concentration in the DFX Ctrough < 10 mcg/mL group was 261.9 μmol/g versus 133.4 μmol/g in the DFX Ctrough > 10 mcg/mL group (p < 0.0001). 21 patients (100%) in the DFX Ctrough > 10 mcg/mL group had ductopenia which was complete in 47.6% of them and severe in 52.4%. All patients with particularly high Ctrough (> 25 mcg/mL) were found to have total ductopenia. 90.5% of all deferasirox-related adverse events and 100% of major adverse events occurred in the DFX Ctrough > 10 mcg/mL group. In the DFX Ctrough < 10 mcg/mL group only one patient interrupted chelation therapy versus 16 (84.2%) patients in the DFX Ctrough > 10 mcg/mL group. We would recommend a close monitoring in pediatric hematopoietic transplant recipients subjected to deferasirox-based therapy because we have observed a high incidence of adverse events and discontinuation of chelation treatment.

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“…observed that twice‐daily DFX administration increased C trough compared with once‐daily route, suggesting that drug levels are dose related. Concerning drug efficacy, Mattioli et al . indicate that a higher plasma DFX concentration could be associated with greater chelation efficacy, suggesting the usefulness to monitor drug concentrations to determine the appropriate dose for each patient.…”

Section: Discussionmentioning

confidence: 99%

Deferasirox pharmacokinetic and toxicity correlation in β-thalassaemia major treatment†

Allegra

Francia

Cusato

et al. 2016

Journal of Pharmacy and Pharmacology

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Determination of deferasirox plasma concentrations: do gender, physical and genetic differences affect chelation efficacy?

Cited by 18 publications

References 22 publications

What is known about deferasirox chelation therapy in pediatric HSCT recipients: two case reports of metabolic acidosis

What is known about deferasirox chelation therapy in pediatric HSCT recipients: two case reports of metabolic acidosis

Safety and tolerability of deferasirox in pediatric hematopoietic stem cell transplant recipients: one facility's five years’ experience of chelation treatment

Deferasirox pharmacokinetic and toxicity correlation in β-thalassaemia major treatment†

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