Efflux transporter substrate determination: bidirectional permeability of acalabrutinib and ACP-5862 across MDCKII cells
P-gp positive control was digoxin, and BCRP positive control was prazosin. Data are the mean ± S.D. of triplicate determinations.
| Acalabrutinib as Substrate | ACP-5862 as Substrate | |||||||
|---|---|---|---|---|---|---|---|---|
| MDCKII | Substrate Concentration | Papp (×10−6 cm/sec) | Efflux | Substrate Concentration | Papp (×10−6 cm/sec) | Efflux | ||
| Cell Line | (µM) | Apical to Basal | Basal to Apical | Ratio | (µM) | Apical to Basal | Basal to Apical | Ratio |
| P-gp | 1 | 1.86 ± 0.20 | 78.8 ± 3.2 | 42.4 | 2 | NA | 60.3 ± 6.4 | NC |
| 10 | 2.22 ± 0.09 | 80.7 ± 1.1 | 36.4 | 10 | 1.15 ± 0.00 | 65.4 ± 5.4 | 57.0 | |
| 30 | 1.96 ± 0.13 | 56.3 ± 0.8 | 28.7 | 50 | 2.28 ± 0.06 | 87.2 ± 6.2 | 38.3 | |
| 1 (+10 µM valspodar) | 24.1 ± 1.1 | 22.6 ± 1.6 | 0.935 | 2 (+10 µM valspodar) | 13.5 ± 1.8 | 27.8 ± 2.0 | 2.05 | |
| 10 (+10 µM valspodar) | 18.0 ± 1.0 | 22.2 ± 1.6 | 1.24 | 10 (+10 µM valspodar) | 15.3 ± 1.2 | 29.2 ± 2.9 | 1.92 | |
| 30 (+10 µM valspodar) | 16.5 ± 0.3 | 16.6 ± 1.7 | 1.01 | 50 (+10 µM valspodar) | 23.7 ± 1.6 | 36.0 ± 4.1 | 1.52 | |
| BCRP | 1 | 8.53 ± 0.49 | 54.2 ± 1.2 | 6.36 | 2 | 4.67 ± 0.08 | 57.7 ± 1.3 | 12.3 |
| 3 | 5.36 ± 0.22 | 45.2 ± 2.4 | 8.44 | 10 | 6.01 ± 0.16 | 61.2 ± 1.8 | 10.2 | |
| 10 | 5.92 ± 0.38 | 48.7 ± 1.9 | 8.23 | 50 | 22.9 ± 1.0 | 74.0 ± 4.8 | 3.23 | |
| 1 (+1 µM Ko143) | 19.0 ± 1.9 | 42.9 ± 8.7 | 2.25 | 2 (+1 µM Ko143) | 24.5 ± 1.2 | 44.1 ± 1.7 | 1.80 | |
| 3 (+1 µM Ko143) | 15.4 ± 1.3 | 35.0 ± 6.6 | 2.27 | 10 (+1 µM Ko143) | 30.8 ± 1.5 | 40.6 ± 1.8 | 1.32 | |
| 10 (+1 µM Ko143) | 16.9 ± 1.6 | 36.9 ± 8.5 | 2.18 | 50 (+1 µM Ko143) | 46.2 ± 2.3 | 49.4 ± 3.7 | 1.07 | |
NC, not counted; Papp, apparent permeability.