Table 4.

Paclitaxel and its monohydroxylated metabolites as determined in bile, plasma, and different tissues of mice with cannulated gall bladder 60 minutes after i.v. administration of [3H]paclitaxel at 5 mg/kg

Biological matrixCompoundStrain
WTMdr1a/1b−/−Mrp2−/−Mdr1a/1b/Mrp2−/−
Plasma*Paclitaxel546 ± 43534 ± 65825 ± 128837 ± 99
[3H] label936 ± 941,068 ± 1601,324 ± 1261,532 ± 111
BilePaclitaxel3.25 ± 0.832.21 ± 0.500.66 ± 0.170.10 ± 0.05
3′-p-Hydroxypaclitaxel0.95 ± 0.331.41 ± 0.330.10 ± 0.05ND
6-α-Hydroxypaclitaxel0.40 ± 0.150.66 ± 0.170.03 ± 0.03ND
[3H] label19.0 ± 3.6422.1 ± 3.024.26 ± 0.433.91 ± 0.92
LiverPaclitaxel27.5 ± 1.6927.0 ± 1.1537.9 ± 4.8636.8 ± 5.73§
3′-p-Hydroxypaclitaxel0.77 ± 0.321.03 ± 0.181.46 ± 0.38§1.76 ± 0.53§
6-α-Hydroxypaclitaxel0.27 ± 0.160.44 ± 0.080.73 ± 0.26§0.74 ± 0.28§
[3H] label24.6 ± 1.1325.4 ± 1.1637.2 ± 3.5839.7 ± 5.13
SICPaclitaxel4.94 ± 0.932.00 ± 0.753.59 ± 0.76§1.63 ± 0.29
3′-p-Hydroxypaclitaxel2.05 ± 0.333.90 ± 1.24§0.70 ± 0.380.86 ± 0.25
6-α-Hydroxypaclitaxel0.28 ± 0.070.55 ± 0.040.14 ± 0.07§0.23 ± 0.14
[3H] label7.55 ± 0.704.28 ± 0.716.60 ± 1.052.78 ± 0.49
  • NOTE: Levels are given as percentage of the dose (mean ± SD, n = 4-6).

    Abbreviations: ND, not detectable; SIC, small intestinal contents.

  • * Plasma levels of paclitaxel are expressed as ng/mL and tritium plasma levels as ng-equivalent/mL. Metabolites were not detectable in plasma at t = 60 minutes.

  • P < 0.01, compared with WT mice.

  • P < 0.001, compared with WT mice.

  • § P < 0.05, compared with WT mice.