TABLE 4

Transport of ximelagatran across Caco-2 cell monolayers in the absence and presence of quinidine or erythromycin

Values are mean and S.D. (n = 3) or the values for two replicates.

Condition
Papp, A-Ba (×10-6 cm/s)
Papp, B-Ab (×10-6 cm/s)
Efflux Ratioc (Papp, B-A/Papp, A-B)
Ximelagatran alone (50 μM) 0.57 (0.06) 19 (1.2) 34
    + Quinidine (100 μM) 2.9 (0.3) 3.4, 3.3 1.2
    + Erythromycin (100 μM) 1.4 (0.07) 16 (0.1) 11
    + Erythromycin (500 μM) 6.4 (0.4) 7.9 (0.5) 1.2
X and M alone (50 μM)d 2.0 (0.2) 45 (1.6) 23
    + Quinidine (100 μM) 7.6 (0.3) 7.6, 7.5 1.0
    + Erythromycin (100 μM) 3.3 (0.1) 38 (1.2) 12
    + Erythromycin (500 μM) 8.3 (0.4) 13 (0.9) 1.6
[3H]Digoxin (27 nM) 1.5 (0.07) 39 (0.8) 26
    + Verapamil (100 μM)
12 (0.9)
12 (0.5)
1.0

  • ↵ a Permeability in apical-to-basolateral direction.

  • ↵ b Permeability in basolateral-to-apical direction.

  • ↵ c Efflux ratio = (Papp, B-A)/(Papp, A-B).

  • ↵ d X and M = total permeability for appearance of ximelagatran plus ethyl-melagatran, hydroxy-melagatran, and melagatran on the receiver side.