TABLE 1

Pharmacokinetic parameters of 14C radioactivity in blood and plasma and of [14C]deferasirox, deferasirox at steady state, and deferasirox-iron complex at steady state in plasma

Data are means ± S.D.; n = 5. Deferasirox and the complex were assayed by cold analysis, [14C]deferasirox by radio-HPLC. Pharmacokinetic parameters represent apparent and descriptive data.

VariableUnitRadioactivity[14C]Deferasirox: PlasmaaDeferasirox (Steady State): PlasmaComplex (Steady State): Plasma
BloodPlasma
tmax (median)h64666
Cmaxμmol/l20.2 ± 10.632.7 ± 18.430.6 ± 15.746.5 ± 22.74.7 ± 3.0
AUC24 hμmol · h/lb,c292 ± 138477 ± 229434 ± 196688 ± 30779 ± 50
% 14C-AUC24 h plasma61 ± 2(100)91 ± 6
% 14C-AUCplasma60 ± 987 ± 219.8 ± 5.2
AUCtμmol · h/lb434 ± 217753 ± 351
t (median)h4872(24)(24)(24)
AUCμmol · h/lb459 ± 207785 ± 355710 ± 291d
% 14C-AUCplasma59 ± 4(100)91 ± 6
t½h12.2 ± 2.89.6 ± 4.011.0 ± 5.39.4 ± 3.6e
Time interval (typical)h12–4812–488–248–24
Accumulation factorf1.60 ± 0.37
  • a [14C]Deferasirox includes iron-complexed deferasirox. Under the conditions of the analytical system the radiolabeled complex cannot be measured separately.

  • b AUC24 h and AUCt were calculated using the linear trapezoidal rule. AUCt–∞ was calculated as Ct · t1/2/ln2.

  • c AUC24 h = AUCss for (cold) deferasirox and complex.

  • d Extrapolated from AUC24 h using extrapolation factor 1.70 (from total 14C).

  • e Individual half-lives of 11 and 25 h were measured in two subjects.

  • f AUCss/AUC24 h of [14C]deferasirox. Corrected for the complex included in [14C]deferasirox the factor is 1.97 ± 0.57.