Table 1.

Plasma pharmacokinetic parameters after oral (10 mg/kg) or i.p. (5 mg/kg) administration of dasatinib

Strain
WTAbcb1a/1b−/−Abcg2−/−Abcb1a/1b;Abcg2−/−
Oral
    AUC(0-6) (mg/L.h)1.02 ± 0.271.70 ± 0.42*1.00 ± 0.352.05 ± 0.25
    Cmax (mg/L)0.37 ± 0.080.49 ± 0.270.31 ± 0.210.70 ± 0.22*
    Tmax (h)20.520.25
    CLapp (L/h.kg)10.4 ± 2.406.15 ± 1.3811.0 ± 3.614.94 ± 0.58
I.p.
    AUC(0-6) (mg/L.h)1.59 ± 0.101.25 ± 0.15*1.69 ± 0.321.52 ± 0.16
    Cmax (mg/L)0.94 ± 0.070.81 ± 0.060.86 ± 0.070.81 ± 0.03*
    t1/2, el (h)0.93 ± 0.041.43 ± 0.490.98 ± 0.281.33 ± 0.12*
    CLapp (L/h.kg)3.16 ± 0.204.05 ± 0.50*3.05 ± 0.663.31 ± 0.36
    Frel (%)32.0 ± 1.7468.0 ± 3.7229.6 ± 2.3967.3 ± 2.13
  • NOTE: Data are means ± SD, n = 5 for oral and n = 4 for i.p. administration. All parameters obtained for KO mice were compared with those for WT mice.

    Abbreviations: Cmax, maximum plasma levels; t1/2, el, elimination half-life, calculated from 2 to 6 h; CLapp, apparent clearance (CL/F); Frel, relative oral bioavailability.

  • * P < 0.05, compared with WT mice.

  • P < 0.01, compared with WT mice.