TABLE 1

Midazolam and sirolimus transport and inhibition across cell monolayers Data shown are the average ± S.D. (n = 3).


Condition

Papp (A→B) × 106

Papp (B→A) × 106

Net Flux Ratio (B→A/A→B)
cm/s
Midazolam (3 μM)
   MDR1-MDCK cells 25 ± 4a 17 ± 1 0.7 ± 0.1
   MDCK cells 16 ± 2 17 ± 4 1.1 ± 0.3
   CYP3A4-transfected Caco-2 18.7 ± 0.9 18.1 ± 0.6 0.97 ± 0.06
      + CsA (10 μM) 21.0 ± 0.7* 19 ± 1 0.88 ± 0.07
      + GG918 (200 nM) 17 ± 1 18 ± 1 1.1 ± 0.1
Midazolam (10 μM)b
   CYP3A4-transfected Caco-2 16.5 ± 0.8 13.3 ± 0.9 0.81 ± 0.07
Sirolimus (1 μM)
   MDR1-MDCK cells 0.043 ± 0.008 3.5 ± 0.4 81 ± 17
   MDCK cells 0.9 ± 0.4 1.4 ± 0.3 1.5 ± 0.7
   CYP3A4-transfected Caco-2 0.29 ± 0.03 0.72 ± 0.03 2.5 ± 0.3
      + CsA (10 μM) 1.77 ± 0.06* 1.50 ± 0.04* 0.85 ± 0.04*
      + GG918 (200 nM) 0.45 ± 0.02* 0.36 ± 0.04* 0.8 ± 0.1*
Sirolimus (20 μM)
   CYP3A4-transfected Caco-2
1.7 ± 0.1
1.20 ± 0.02
0.70 ± 0.05
  • * p < 0.05 (relative to control treatment in that cell line)

  • a Permeability calculated up to 24 min instead of 36 min for this direction due to the nonlinearity beyond this point

  • b Permeability calculated at 1 h for this experiment