Table 1.

Summary of topotecan pharmacokinetic parameters in wild-type and transporter-deficient mice treated with topotecan alone or with topotecan plus gefitinib

ParameterTreatmentP
TopotecanTopotecanTopotecan + gefitinib
Abcg2+/+Abcg2−/−Abcg2−/−(+/+) vs (−/−)Gefitinib vs without
CL (L/h/m2)15.4 (1.6)11.3 (2.2)8.3 (2.5)0.0060.008
Vc (L/m2)5.75 (0.8)
F0.11 (0.02)0.22 (0.06)0.47 (0.11)0.060.006
Kcp (h−1)0.50 (0.12)
Kpc (h−1)0.62 (0.09)
Ka (h−1)2.35 (0.40)
Mdr1(a/b)+/+Mdr1(a/b)−/−Mdr1(a/b)−/−(+/+) vs (−/−)Gefitinib vs without
CL (L/h/m2)15.5 (0.97)12.2 (1.5)10.2 (1.4)0.0040.04
Vc (L/m2)4.9 (0.47)
F0.21 (0.02)0.30 (0.04)0.50 (0.10)0.010.03
Kcp (h−1)0.32 (0.04)1.45 (0.41)0.29 (0.57)0.0060.004
Kpc (h−1)0.68 (0.06)
Ka (h−1)2.02 (0.48)
SCIDSCIDGefitinib vs without
CL (L/h/m2)42.2 (4.6)22.5 (7.2)0.0004
Vc (L/m2)19.2 (3.7)
F0.35 (0.09)0.61 (0.14)0.02
Kcp (h−1)0.59 (0.19)
Kpc (h−1)0.18 (0.07)
Ka (h−1)1.43 (0.42)4.41 (0.86)0.00008
  • NOTE: Data are presented as mean (SE). —, no significant difference.