Kinetic parameters for the transcellular transport in LLC-PK1 and LLC-GA5-COL150 cells
The transport of [14C]bepotastine, fexofenadine, and [3H]digoxin across LLC-PK1 and LLC-GA5-COL150 monolayers in the presence or absence of P-gp inhibitor was evaluated, the amount transported to the receiver side in the A-to-B and B-to-A direction for 2 h after adding the drugs. Each value represents the mean ± S.E.M. of three to six experiments.
Condition | LLC-PK1 Papp (1 × 10-6 cm/s) | LLC-GA5-COL150 Papp (1 × 10-6 cm/s) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A-to-B | B-to-A | Flux Ratio | A-to-B | B-to-A | Flux Ratio | CFR | ||||||
| [14C]Bepotastine (5 μM) | 5.87 ± 0.14 | 4.51 ± 0.31 | 0.77 ± 0.03 | 1.57 ± 0.04 | 6.30 ± 0.26 | 4.00 ± 0.10a | 5.26 ± 0.22 | |||||
| [14C]Bepotastine (500 μM) | 5.18 ± 0.13 | 3.98 ± 0.27 | 0.77 ± 0.03 | 1.81 ± 0.04 | 5.56 ± 0.23 | 3.06 ± 0.07a | 4.03 ± 0.19b | |||||
| [14C]Bepotastine (5 μM) + cyclosporin A (10 μM) | 4.78 ± 0.35 | 3.93 ± 0.23 | 0.82 ± 0.01 | 2.81 ± 0.07 | 3.70 ± 0.66 | 1.31 ± 0.23 | 1.60 ± 0.32b | |||||
| [14C]Bepotastine (5 μM) + verapamil (100 μM) | 4.65 ± 0.21 | 3.99 ± 0.18 | 0.86 ± 0.04 | 2.43 ± 0.14 | 3.53 ± 0.29 | 1.45 ± 0.25 | 1.71 ± 0.43b | |||||
| Fexofenadine (5 μM) | 0.77 ± 0.02 | 0.80 ± 0.04 | 1.04 ± 0.05 | 0.19 ± 0.03 | 0.72 ± 0.01 | 3.90 ± 0.63a | 3.91 ± 1.04 | |||||
| [3H]Digoxin (20 nM) | 3.66 ± 0.08 | 6.30 ± 0.35 | 1.74 ± 0.09 | 0.78 ± 0.02 | 15.26 ± 0.51 | 19.49 ± 0.58a | 11.36 ± 0.08 | |||||
↵ a Statistical difference of the flux ratio between LLC-PK1 and LLC-GA5-COL150 cells was assessed by Student's t test (P < 0.05).
↵ b Statistical difference of the corrected flux ratio (CFR) compared with that of [14C]bepotastine (5 μM) in the presence of excessive bepotastine, and P-gp inhibitor was assessed by Student's t test (P < 0.05).