Tab. 2: Donor-specific effects of RAP on 1α,25(OH)2D3-mediated induction of 24,25(OH)2D3 formation clearance.
Treatment with the megalin inhibitor (RAP) significantly reduced the maximal inducibility (Emax) for the 1α,25(OH)2D3-mediated induction of 24,25(OH)2D3 formation clearance in the PT-MPS but had no significant effect on the concentration of 1α,25(OH)2D3 required for halfmaximal induction (EC50) of 24,25(OH)2D3 formation clearance.
| EC50 (nM) | Emax (% Increase from baseline) | |||||
|---|---|---|---|---|---|---|
| Donor No. | No RAP | RAP | Fold-change EC50 |
No RAP | RAP | Fold-change Emax |
| 1 | 62 | 130 | 2.1 ↑ | 5300 | 3500 | 1.5 ↓ |
| 2 | 25 | 56 | 2.2 ↑ | 990 | 640 | 1.5 ↓ |
| 3 | 5.3 | 170 | 32 ↑ | 800 | 280 | 2.9 ↓ |
| 4 | 240 | 130 | 1.8 ↓ | 5900 | 2300 | 2.6 ↓ |
| 5 | 5.6 | 0.61 | 9.2 ↓ | 235 | 200 | 1.2 ↓ |
| Mean† | 68 | 97 | 1.5 ↑ | 2600 | 1400 | *1.8 ↓ |
| SD† | 99 | 68 | 8.1 | 2700 | 1500 | 1.5 |
†
Geometric mean and geometric standard deviation calculated for “fold-change” (ratio) parameters.
*
, p < 0.05.