TABLE 4

Concentration ratios of four compounds at two time points in Mdr1a/1b(-/-), (-/-), Bcrp(-/-), and Mdr1a/1b(-/-), (-/-)Bcrp(-/-) mice vs. concentrations in FVB mice after s.c. administration

Data are presented as mean ± S.D. from three to five male mice.



Mdr1a/1b(-/-), (-/-) vs. FVB

Bcrp(-/-) vs. FVB

Mdr1a/1b(-/-), (-/-)Bcrp(-/-) vs. FVB

Brain
Plasma
CSF
Brain/Plasma
Brain
Plasma
CSF
Brain/Plasma
Brain
Plasma
CSF
Brain/Plasma
0.5 h
    Flavopiridol 1.79 ± 0.27 1.06 ± 0.17 1.85 ± 0.21 1.67 ± 0.15 1.42 ± 0.33 1.09 ± 0.28 1.51 ± 0.41 1.29 ± 0.11 10.07 ± 1.87***,### 1.35 ± 0.12* 5.81 ± 1.56**,## 7.35 ± 1.41**,##
    Imatinib 3.37 ± 0.35 0.76 ± 0.10 1.54 ± 0.34 4.45 ± 0.79 0.89 ± 0.19 0.94 ± 0.09 1.11 ± 0.41 0.94 ± 0.14 19.03 ± 4.27**,## 0.69 ± 0.11## 5.80 ± 1.19**,### 28.23 ± 8.81**,##
    PF-407288 0.98 ± 0.34 0.66 ± 0.20 0.78 ± 0.41 1.53 ± 0.40 1.13 ± 0.33 0.79 ± 0.18 0.45 ± 0.18 1.43 ± 0.14 2.70 ± 0.83**,# 1.34 ± 0.28**,## 1.88 ± 0.63*,## 2.02 ± 0.31##
    Prazosin 2.26 ± 0.66 1.24 ± 0.33 2.47 ± 1.09 1.86 ± 0.42 1.23 ± 0.09 0.92 ± 0.16 0.83 ± 0.38 1.38 ± 0.32 5.67 ± 0.79***,### 0.96 ± 0.30 5.24 ± 1.89*,## 6.14 ± 1.19**,###
2 h
    Flavopiridol 2.72 ± 1.13 1.92 ± 1.01 4.45 ± 1.82 1.58 ± 0.42 1.86 ± 0.35 1.42 ± 0.34 2.51 ± 0.90 1.33 ± 0.09 16.85 ± 3.40***,### 2.50 ± 0.68# 15.35 ± 7.25*,# 6.89 ± 0.95***,###
    Imatinib 3.83 ± 1.18 0.90 ± 0.35 N.E. 4.46 ± 1.07 0.84 ± 0.38 0.98 ± 0.31 N.E. 0.86 ± 0.32 50.78 ± 6.96***,### 0.92 ± 0.36# N.E. 63.59 ± 31.78*,#
    PF-407288 2.10 ± 1.18 1.94 ± 0.65 N.E. 1.02 ± 0.22 1.70 ± 0.26 1.43 ± 0.29 N.E. 1.19 ± 0.17 2.66 ± 0.86 1.93 ± 0.60 N.E. 1.36 ± 0.23*
    Prazosin
4.33 ± 1.06
2.42 ± 0.57
1.42 ± 0.10
1.75 ± 0.24
3.62 ± 0.33
3.20 ± 0.36
0.43 ± 0.57
1.10 ± 0.04
22.67 ± 2.25***,###
4.33 ± 0.73**,#
8.77 ± 3.58*,##
5.18 ± 0.78***,###
  • N.E., not estimated.

    Comparison of concentration ratios of Mdr1a/1b(-/-), (-/-), Bcrp(-/-) vs. FVB and concentration ratios of Mdr1a/1b(-/-), (-/-) vs. FVB: * P < 0.05; ** P < 0.01; *** P < 0.001.

    Comparison of concentration ratios of Mdr1a/1b(-/-), (-/-), Bcrp(-/-) vs. FVB and concentration ratios of Bcrp(-/-) vs. FVB: # P < 0.05; ## P < 0.01; ### P < 0.001.