TABLE 1

Bidirectional flux of trametinib in MDCKII-WT, MDCKII-Bcrp1, and MDCKII-WT, and MDCKII-MDR1-transfected cells

Cell Line (MDCKII)PappEfflux RatioCorrected Flux Ratio
A-to-BB-to-A
×10–6 cm/sec
WT (BCRP)12.8 ± 2.512.3 ± 4.70.96—
WT (BCRP) +0.2 μM KO-14312.5 ± 0.912.6 ± 1.01
Inulina0.93 ± 0.380.37 ± 0.260.4
BCRP5.17 ± 2.1b19.3 ± 1.9 b3.73.85
BCRP + 0.2 μM KO-14311.7 ± 2.612.2 ± 1.61.04
Inulina0.9 ± 0.320.93 ± 0.211.03
WT (MDR1)17.8 ± 1.818.6 ± 4.31.04—
WT (MDR1) + 1 μM LY3359798.6 ± 4.911.3 ± 1.21.3
Inulina0.12 ± 0.120.24 ± 0.142
MDR113.8 ± 8 b35.2 ± 1.7 b2.552.45
MDR1 + 1 μM LY3359799.3 ± 1.711.4 ± 2.91.23
Inulina0.5 ± 0.260.62 ± 0.191.24

  • ↵a Percent transported at 120 minutes was less than 1%.

  • ↵b Significantly different compared with respective wild-type controls.