Table 1.
Estimated Ki for SGLT2 and SGLT1 transporters,8 the ratio between the proximal tubule segment concentration of a gliflozin and respective SGLT Ki, and model‐predicted peak and average compound concentration in the plasma, kidney (S1/S2 and S3), and bladder
| Means of estimation | Dapagliflozin (10 mg) | Empagliflozin (25 mg) | Canagliflozin (300 mg) | |
|---|---|---|---|---|
| Ki,SGLT2 (nM) | Fitted | 0.031 | 0.195 | 0.111 |
| Ki,SGLT1 (nM) | Calculated | 36.35 | 243.03 | 17.55 |
| SGLT2:SGLT1 | Calculated | 1,200‐fold | 1,300‐fold | 160‐fold |
| Cmax (nM) | ||||
| Plasma | Predicted | 275 | 533 | 6,156 |
| S1–S2 | 52.5 | 260 | 137 | |
| S3 | 196 | 976 | 513 | |
| Bladder | 987 | 8,172 | 3,922 | |
| Cmax,S1S2:Ki,SGLT2 | Calculated | 1,700‐fold | 1,300‐fold | 1,200‐fold |
| Cmax,S3:Ki,SGLT1 | 5.4‐fold | 4.0‐fold | 29‐fold | |
| Cavg,0–24 (nM) | ||||
| Plasma | Predicted | 51.7 | 229 | 2109 |
| S1/S2 | 9.87 | 112 | 46.9 | |
| S3 | 37.0 | 420 | 176 | |
| Bladder | 462 | 5164 | 2205 | |
| Cavg,0–24,S1S2:Ki,SGLT2 | Calculated | 320‐fold | 570‐fold | 420‐fold |
| Cavg,0–24,S3:Ki,SGLT1 | 1.0‐fold | 1.7‐fold | 10‐fold | |
Fold calculations were rounded to two decimals.
Cavg, 0‐24, a model‐predicted average concentration of the compound during 24‐hours period after dose administration; Cmax, a model‐predicted peak concentration of the compound; K i, inhibitory constant; S1, segment 1 of the proximal tubule, a location of SGLT2; S2, segment 2 of the proximal tubule, a location of SGLT2; S3, segment 3 of the proximal tubules, a location of SGLT1; SGLT1, sodium‐glucose cotransporter 1; SGLT2, sodium‐glucose cotransporter 2.