Table 1.
Mean ± SD pharmacokinetic parameters and the ratio of mean pharmacokinetic parameters (preprandial/fasting) in subjects who received 5 mg luseogliflozin in the SAD study, and mean ± SD pharmacokinetic parameters in the MAD study
| SAD study | ||||
|---|---|---|---|---|
| Condition: | Fasting | |||
| Dose: | 1 mg (N = 3) | 3 mg (N = 8) | 5 mg (N = 8) | 9 mg (N = 8) |
| C max (ng/mL) | 38.2 ± 4.86 | 116 ± 24.6 | 187 ± 27.3 | 312 ± 45.2 |
| T max (h) | 0.667 ± 0.289 | 0.750 ± 0.267 | 1.06 ± 0.496 | 1.25 ± 0.598 |
| AUClast (ng∙h/mL)a | 323 ± 47.9 | 973 ± 243 | 1,770 ± 290 | 2,960 ± 315 |
| AUCinf (ng∙h/mL) | 337 ± 51.9 | 1,000 ± 260 | 1,830 ± 322 | 3,050 ± 326 |
| λz (1/h) | 0.0666 ± 0.00350 | 0.0758 ± 0.00749 | 0.0722 ± 0.00858 | 0.0705 ± 0.00502 |
| T 1/2 (h) | 10.4 ± 0.552 | 9.23 ± 0.950 | 9.72 ± 1.17 | 9.87 ± 0.720 |
| CL/F (L/h) | 3.02 ± 0.489 | 3.16 ± 0.744 | 2.80 ± 0.465 | 2.98 ± 0.326 |
| Vd/F (L) | 45.3 ± 6.88 | 41.4 ± 7.17 | 38.7 ± 4.11 | 42.4 ± 5.40 |
| Condition: | Fasting | Preprandial | Preprandial/fastingb | |
|---|---|---|---|---|
| Dose: | 15 mg (N = 8) | 25 mg (N = 8) | 5 mg (N = 8) | 5 mg (N = 8) |
| C max (ng/mL) | 544 ± 143 | 721 ± 123 | 205 ± 53.5 | 107 (89.9–127) |
| T max (h) | 1.56 ± 1.02 | 2.25 ± 1.46 | 0.750 ± 0.535 | – |
| AUClast (ng∙h/mL)a | 5,120 ± 836 | 8,480 ± 1,180 | 1,860 ± 267 | 105 (101–109) |
| AUCinf (ng∙h/mL) | 5,140 ± 834 | 8,510 ± 1,180 | 1,930 ± 290 | 105 (101–110) |
| λz (1/h) | 0.0564 ± 0.0173 | 0.0562 ± 0.00904 | 0.0682 ± 0.00726 | – |
| T 1/2 (h) | 13.8 ± 5.76 | 12.6 ± 2.13 | 10.3 ± 1.02 | – |
| CL/F (L/h) | 2.99 ± 0.483 | 2.99 ± 0.436 | 2.64 ± 0.362 | – |
| Vd/F(L) | 60.5 ± 31.0 | 54.7 ± 13.7 | 38.9 ± 4.97 | – |
| MAD study | ||||
|---|---|---|---|---|
| Dose: | 5 mg (N = 8) | 10 mg (N = 8) | ||
| Day: | Day 1 | Day 7 | Day 1 | Day 7 |
| C max (ng/mL) | 214 ± 52.0 | 248 ± 45.1 | 409 ± 84.3 | 475 ± 111 |
| T max (h) | 0.625 ± 0.354 | 0.625 ± 0.231 | 0.500 ± 0.00 | 0.563 ± 0.177 |
| AUC (ng∙h/mL)c | 1,930 ± 435 | 1,980 ± 382 | 3,430 ± 814 | 3,470 ± 778 |
| λz (1/h) | 0.0676 ± 0.0118 | 0.0668 ± 0.0119 | 0.0762 ± 0.00677 | 0.0768 ± 0.00897 |
| T 1/2 (h) | 10.5 ± 2.02 | 10.7 ± 2.40 | 9.15 ± 0.746 | 9.14 ± 1.11 |
| CL/F (L/h) | 2.72 ± 0.648 | 2.61 ± 0.537 | 3.05 ± 0.628 | 3.00 ± 0.612 |
| Vd/F (L) | 40.3 ± 6.67 | 39.3 ± 5.12 | 40.1 ± 8.36 | 38.8 ± 5.70 |
AUC area under the concentration–time curve, AUC inf AUC from 0 to infinity, AUC last AUC from 0 to the last quantifiable data point, AUC τ AUC during 0–24 h after administration, CL/F apparent clearance, C max maximum concentration, λz elimination rate constant, MAD multiple ascending dose, SAD single ascending dose, T 1/2 elimination half-life, T max time to maximum concentration, Vd/F apparent volume of distribution
a1–9 mg; 0–48 h, 15–25 mg; 0–96 h
bEstimated value (90% CI)
cDay1: AUCinf; Day7: AUCτ