Table 1.

Plasma pharmacokinetic variables after oral or i.v. administration of paclitaxel at 10 mg/kg

Strain
WTMdr1a/1b−/−Mrp2−/−Mdr1a/1b/Mrp2−/−
Oral
    AUC(0-8) (h.mg/L)0.44 ± 0.193.75 ± 0.38*0.40 ± 0.086.23 ± 0.60*
    Cmax (mg/L)0.13 ± 0.111.05 ± 0.19*0.12 ± 0.041.53 ± 0.19*
    t1/2, el (h)1.96 ± 0.281.69 ± 0.161.74 ± 0.112.42 ± 0.28
i.v.
    AUC(0-8) (h.mg/L)5.57 ± 0.267.08 ± 0.317.33 ± 0.349.41 ± 0.57§
    Cmax (mg/L)6.17 ± 0.217.09 ± 0.306.89 ± 0.896.17 ± 0.68
    t1/2, el (h)1.65 ± 0.111.79 ± 0.101.61 ± 0.112.08 ± 0.12
    Cl (L/h.kg)1.80 ± 0.081.41 ± 0.061.36 ± 0.061.06 ± 0.06§
    F (%)7.9 ± 3.453.0 ± 5.8§5.5 ± 1.166.2 ± 7.5§
  • NOTE: t1/2, el is calculated from 2 to 8 hours for both oral and i.v. administration. Data are mean ± SD, n = 5-6 for oral and n = 3-4 for i.v. administration.

    Abbreviations: AUC(0-8), AUC up to 8 hours; Cl, plasma clearance; F, oral bioavailability.

  • * P < 0.001, compared with WT mice.

  • P< 0.01, compared with Mdr1a/1b−/− mice.

  • P < 0.05, compared with WT mice.

  • § P < 0.01, compared with WT mice.