Simultaneous Determination of Plasma Deferasirox and Deferasirox-Iron Complex Using an HPLC-UV System and Pharmacokinetics of Deferasirox in Patients With β-Thalassemia Major: Once-daily Versus Twice-daily Administration

Purpose: Deferasirox (DEFR), when administered BID, improves iron overload and decreases DEFR-related adverse effects in patients with beta-thalassemia major. However, the pharmacokinetic (PK) disposition of DEFR and the iron DEFR complex (Fe-[DEFR](2)) in this dosing strategy is unclear. Methods: Chromatographic analysis was performed using a solvent delivery system coupled to an HPLC-UV detector to determine the steady-state concentrations of DEFR (C-DEFR) and Fe-(DEFR)(2) (CFe-[DEFR.]2) in beta-thalassemia major patients (n = 8) following either once-daily or BID dosing, during which the PK parameters of the 2 dosing schedules were compared. Findings: An HPLC-UV system for the analysis of blood samples following solid-phase extraction was validated. Patients who received 40 mg/kg of DEFR had higher mean CDEFR and CFe-[DEFR]2 values at all sampling times. However, concentrations of iron-DEFR complex were similar in patients who received 30 or 40 mg/kg of DEFR in the once-daily group at the 6- to 24-hour sampling times. There was no significant difference in any of the PK parameters; however, DEFR administration BID increased the mean trough levels of DEFR (183.8 [157.5] mu mol/L) compared with once daily (87.7 [56.8] mu mol/L), whereas all the patients had increased peak levels per individual DEFR dose when they were switched from once daily to BID (139.0 [59.8] mu mol/L vs 289.2 [145.8] mu mol/L, respectively). (C) 2015 Elsevier HS Journals, Inc. All rights reserved.