Table 6.

Part II: pharmacokinetic variables of total (lactone plus carboxylate) topotecan

Total topotecan
ABCD
Cycle 1
    Dose (mg)1.01.52.02.5
    n3363
    AUC* (μg·h/L)39.2 (13.6-113.4)49.7 (26.3-94.1)51.0 (24.6-105.8)98.9 (30.4-321.1)
    %CV38276151
    CL/F (L/h)25.5 (8.8-73.6)30.2 (15.9-57.1)39.2 (18.9-81.4)25.3 (7.8-82.1)
    Cmax (μg/L)4.5 (2.4-8.7)8.1 (4.1-16.2)8.0 (4.2-15.3)14.2 (7.2-28.1)
    kel (h−1)0.160 (0.075-0.341)0.190 (0.079-0.457)0.231 (0.165-0.325)0.156 (0.118-0.205)
    Vd/F (L)159 (54-473)159 (83-306)169 (92-313)163 (66-402)
    t1/2 (h)4.33 (2.03-9.21)3.65 (1.52-8.79)2.99 (2.14-4.20)4.46 (3.38-5.88)
    Tmax (h)4.03 (2.00-4.03)1.90 (1.50-2.08)2.00 (2.00-4.00)4.00 (2.03-4.25)
Cycle 2
    Dose (mg)1.01.52.02.5
    n1361
    AUC* (μg·h/L)28.158.7 (23.0-150.0)70.9 (44.0-114.0)65.4
    %CV4153
    CL/F (L/h)35.625.5 (10.0-65.3)28.2 (17.5-45.4)38.2
    Cmax (μg/L)4.48.8 (3.2-24.1)9.7 (5.6-17.0)11.2
    kel (h−1)0.2610.170 (0.105-0.276)0.159 (0.137-0.185)0.166
    Vd/F (L)136150 (38-596)177 (122-257)230
    t1/2 (h)2.654.07 (2.51-6.60)4.35 (3.75-5.05)4.17
    Tmax (h)4.002.00 (2.00-2.23)4.00 (2.00-6.03)2.00
  • NOTE: Data are presented as mean ± SD. F followed from part I elacridar simultaneously with topotecan (see Table 5).

  • * Determined by calculation of AUC by the linear-logarithmic trapezoid method up to the last measured time point with extrapolation to infinity using the terminal rate constant kel.