The pharmacokinetic and safety profile of single-dose deferiprone in subjects with sickle cell disease

Denis Soulières, Jules Mercier-Ross, Caroline Fradette, Anna Rozova, Yu Chung Tsang, Fernando Tricta, Denis Soulières, Jules Mercier-Ross, Caroline Fradette, Anna Rozova, Yu Chung Tsang, Fernando Tricta

Abstract

Patients with sickle cell disease (SCD) who undergo repeated blood transfusions often develop iron overload. Deferiprone (Ferriprox®) is an oral iron chelator indicated for the treatment of transfusional iron overload due to thalassemia syndromes and has been recently approved as a treatment for iron overload in adult and pediatric patients with SCD and other anemias. The present study aims to characterize the pharmacokinetic (PK) profile of deferiprone (DFP) in adult subjects with SCD. In this phase I, open-label study, subjects with SCD were administered a single 1500 mg dose of DFP. Blood and urine samples were collected for PK assessments of DFP and its main metabolite, deferiprone 3-O-glucuronide (DFP-G). Eight subjects were enrolled and completed the study. Following drug administration, serum levels of DFP and DFP-G rose to maximum concentrations at 1.0 and 2.8 h post-dose, respectively. The half-lives of DFP and DFP-G were 1.5 and 1.6 h, respectively. The majority of administered drug was metabolized and excreted as DFP-G, with less than 4% excreted unchanged in urine up to 10 h post-dose. Subjects received a safety assessment 7 (± 3) days post-dose. Two subjects reported mild adverse events unrelated to the study drug, and no other safety concerns were reported. The PK profile of DFP in SCD subjects is consistent with previous reports in healthy adult volunteers, suggesting no special dosing adjustments are indicated for this population. These findings provide valuable insight for treating iron overload in patients with SCD, who have limited chelation therapy treatment options (trial registration number: NCT01835496, date of registration: April 19, 2013).

Keywords: Deferiprone; Iron chelation; Pharmacokinetics; Sickle cell disease.

Conflict of interest statement

Denis Soulières is a participant on ApoPharma advisory board and received ApoPharma institutional grant.

Jules Mercier-Ross has no conflict of interest to declare.

Caroline Fradette is an employee of Chiesi Canada.

Anna Rozova is an employee of Chiesi Canada.

Yu Chung Tsang is an employee of Apotex Inc., which is the contract manufacturer of the drug product (i.e., FERRIPROX®) used in the study reported in this manuscript.

Fernando Tricta is an employee of Chiesi Canada.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
a Serum concentrations of deferiprone and b deferiprone 3-O-glucuronide following a 1500 mg dose of deferiprone
Fig. 2
Fig. 2
a Cumulative % dose of deferiprone and b deferiprone 3-O-glucuronide excreted following a 1500 mg dose of deferiprone

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