Table 4.

Summary of topotecan and lapatinib pharmacokinetics

DrugTopotecan alone (day 1)*Lapatinib + topotecan (day 8)*Day 8:day 1 ratio†
Topotecan (n = 9)
    Cmax (ng/mL)162 (146-178)128 (102-154)0.79 (0.66-0.92)
    AUC0-24 h (h·ng/mL)432 (329-535)510 (323-697)1.18 (1.07-1.29)
    CLp (L/h/m2)7.28 (5.35-8.91)6.14 (4.27-8.01)0.84 (0.76-0.92)
    CLNRF (L/h/m2)5.25 (3.99-6.51)4.11 (2.72-5.50)0.78 (0.68-0.88)
    t1/2 (h)4.30 (4.09-4.51)4.35 (3.96-4.74)1.01 (0.96-1.06)
    Vss (L/m2)30.5 (26.5-34.5)30.1 (23.9-36.3)0.99 (0.90-1.08)
Lapatinib alone (day 7)*
Lapatinib + topotecan (day 8)*
Day 8:day 7 ratio†
Lapatinib (n = 9)
    Cmax (μg/mL)1.89 (1.33-2.68)2.33 (1.78-3.05)1.24 (1.00-1.52)
    Tmax (h)3.00 (2.59-8.00)‡4.00 (1.50-12.0)‡0.25 (−4.00 to 9.00)§
    AUC0-24 h (h·μg/mL)23.3 (14.5-37.3)31.7 (22.6-44.5)1.36 (1.04-1.78)

  • ↵* Geometric mean and 95% confidence intervals unless otherwise indicated.

  • ↵† Geometric least squares mean ratio and 90% confidence intervals unless otherwise indicated.

  • ↵‡ Median and range.

  • ↵§ Median and range of pairwise differences.