Table 2.

Levels of paclitaxel and monohydroxylated metabolites in plasma and liver at t = 8 hours after i.v. administration of 10 mg/kg paclitaxel

Biological matrixCompoundStrain
WTMdr1a/1b−/−Mrp2−/−Mdr1a/1b/Mrp2−/−
Plasma (ng/mL)Paclitaxel38.3 ± 5.880.5 ± 8.9*73.9 ± 12.6189.6 ± 13.1
3′-p-HydroxypaclitaxelND2.3 ± 0.42.0 ± 0.56.5 ± 0.79
6-α-HydroxypaclitaxelND0.6 ± 0.71.0 ± 0.74.4 ± 1.5
Liver (% dose)Paclitaxel5.8 ± 0.89.3 ± 1.0*9.2 ± 1.512.3 ± 1.6*
3′-p-Hydroxypaclitaxel0.3 ± 0.040.5 ± 0.08*1.8 ± 0.34.1 ± 0.4
6α-HydroxypaclitaxelND0.1 ± 0.020.5 ± 0.34.4 ± 0.3
  • NOTE: Plasma levels of paclitaxel and metabolites are expressed as ng/mL (mean ± SD, n = 3-4) and liver levels of paclitaxel and metabolites are expressed as percentage of the dose (mean ± SD, n = 3-4).

    Abbreviation: ND, not detectable.

  • * P < 0.01, compared with WT mice.

  • P < 0.05, compared with WT mice.

  • P < 0.001, compared with WT mice.