TABLE 1

Pharmacokinetic parameters in plasma after intravenous and p.o. administration of [14C]deferasirox and intravenous administration of [14C]Fe(deferasirox)2 (mean of n = 3 rats each)

Compound Administered
[14C]Deferasirox
[14C]Fe(deferasirox)2
[14C]Deferasirox
[14C]Deferasirox
14C
DF
DF Complex
14C
DF
DF Complex
14C
DF
DF Complex
14C
DF
DF Complex
Dose, route 10 mg/kg, i.v. 10 mg/kg, i.v. 10 mg/kg, p.o. 100 mg/kg, p.o.
Tmax, h 0.08 0.08 1 0.08 0.08 0.08 0.5 0.5 2 8 1 4
Cmax, μg/mla 22.9 25.3 2.03 91.7 1.57 90.0 3.18 2.65 0.49 56.4 52.6 6.11
C0, μg/mla N.C. 29.1 N.C. N.C. 128 N.C. 0 0 0 0 0 0
AUC, μg/ml · ha 30.5 29.7 4.23 57.3 5.4 42.4 15.0 7.62 5.79 879 807 79.0
Vss, l/kg N.C. 0.46 N.C. N.C. 0.084 N.C. N.C. N.C. N.C. N.C. N.C. N.C.
CL, ml/kg/min N.C. 6.20 N.C. N.C. 4.0 N.C. N.C. N.C. N.C. N.C. N.C. N.C.
MRT, h N.C. 1.25 N.C. N.C. 0.35 N.C. N.C. N.C. N.C. N.C. N.C. N.C.
t½, hb
 N.C.
0.7
N.C.
N.C.
0.4
N.C.
N.C.
(0.5)c
N.C.
N.C.
N.C.
N.C.

  • DF, deferasirox; DF complex, Fe(deferasirox)2; N.C., not calculated

  • ↵ a To convert concentration data from mass units (μg/ml for defined compounds, μg-Eq/ml for 14C concentrations) to molar units (μmol/ml), divide by 373.4 (deferasirox) or 865.5 [Fe(deferasirox)2]

  • ↵ b For deferasirox after intravenous dosing, a time range of 5 min to 4 h and for Fe(deferasirox)2 of 5 min to 2 h was considered

  • ↵ c For the initial elimination phase for deferasirox after p.o. dosing, the time range from 1 to 2 h was considered. This half-life is only a descriptive estimate because of the low number of sampling time points