Table 10.
Simulated pharmacokinetic parameters for simvastatin, s‐warfarin, bupropion or repaglinide with and without canagliflozin (300 mg) in healthy human subjects
| Simulated pharmacokinetic parameters of simvastatin (40 mg) in virtual subjects (n = 100) | ||||||||
|---|---|---|---|---|---|---|---|---|
| Simvastatin without canagliflozin | Simvastatin with canagliflozin | Ratio with canagliflozin over without canagliflozin | ||||||
| AUC0‐48h (ng h ml−1) | Tmax (h) | Cmax (ng ml−1) | AUC0‐48h (ng h ml−1) | Tmax (h) | Cmax (ng ml−1) | AUC ratio | Cmax ratio | |
| Mean | 24.41 | 1.35 | 5.40 | 27.58 | 1.39 | 6.03 | 1.13 | 1.12 |
| 5th percentile | 5.26 | 0.90 | 1.07 | 6.11 | 0.95 | 1.19 | 1.09 | 1.07 |
| 95th percentile | 67.01 | 1.85 | 15.22 | 78.58 | 1.86 | 16.70 | 1.20 | 1.19 |
| CV (%) | 86 | 23 | 85 | 85 | 21 | 84 | 3.0 | 3.0 |
| SD | 20.92 | 0.31 | 4.59 | 23.42 | 0.29 | 5.07 | 0.03 | 0.04 |
| Simulated pharmacokinetic parameters of s‐warfarin (15 mg) in virtual subjects (n = 20) | ||||||||
|---|---|---|---|---|---|---|---|---|
| S‐warfarin without canagliflozin | S‐warfarin with canagliflozin | ratio with canagliflozin over without canagliflozin | ||||||
| AUC (ng h ml−1) | Tmax (h) | Cmax (ng ml−1) | AUC (ng h ml−1) | Tmax (h) | Cmax (ng ml−1) | AUC ratio | Cmax ratio | |
| Mean | 45 662.23 | 2.57 | 1522.60 | 46 270.15 | 2.60 | 1528.59 | 1.01 | 1.00 |
| 5th percentile | 14 608.29 | 1.99 | 731.39 | 14 790.17 | 1.99 | 734.10 | 1.01 | 1.00 |
| 95th percentile | 90 662.77 | 3.61 | 2606.95 | 92 839.30 | 3.61 | 2618.17 | 1.02 | 1.00 |
| CV (%) | 63.00 | 22.00 | 42.00 | 63.00 | 22.00 | 42.00 | ||
| SD | 28590.11 | 0.57 | 640.55 | 28984.54 | 0.57 | 643.18 | ||
| Simulated pharmacokinetic parameters of bupropion (150 mg) in virtual subjects (n = 100) | ||||||||
|---|---|---|---|---|---|---|---|---|
| Bupropion without canagliflozin | Bupropion with canagliflozin | Ratio with canagliflozin over without canagliflozin | ||||||
| AUC0‐24h (ng h ml−1) | Tmax (h) | Cmax (ng ml−1) | AUC0‐24h (ng h ml−1) | Tmax (h) | Cmax (ng ml−1) | AUC ratio | Cmax ratio | |
| Mean | 1374.90 | 1.76 | 223.77 | 1503.70 | 1.81 | 244.66 | 1.13 | 1.12 |
| 5th percentile | 296.88 | 1.18 | 69.51 | 349.13 | 1.25 | 81.49 | 1.03 | 1.03 |
| 95th percentile | 4248.25 | 2.74 | 501.93 | 4393.12 | 2.75 | 561.87 | 1.22 | 1.24 |
| CV (%) | 0.0 | 27 | 0.0 | 0.0 | 26 | 0.0 | 5.0 | 6.0 |
| SD | 1292.81 | 0.48 | 150.55 | 1331.18 | 0.46 | 155.56 | 0.06 | 0.06 |
| Simulated pharmacokinetic parameters of repaglinide (0.25 mg) in virtual subjects (n = 100) | ||||||||
|---|---|---|---|---|---|---|---|---|
| Repaglinide alone | Repaglinide + canagliflozin | Ratio with canagliflozin over without canagliflozin | ||||||
| AUC0‐24h (ng h ml−1) | Tmax (h) | Cmax (ng ml−1) | AUC0‐24h (ng h ml−1) | Tmax (h) | Cmax (ng ml−1) | AUC0‐24h | Cmax | |
| Mean | 6.66 | 0.34 | 3.82 | 6.98 | 0.36 | 3.88 | 1.04 | 1.02 |
| 5th percentile | 1.92 | 0.19 | 1.63 | 1.97 | 0.20 | 1.65 | 1.02 | 1.00 |
| 95th percentile | 13.2 | 0.55 | 6.36 | 13.9 | 0.60 | 6.41 | 1.09 | 1.04 |
| CV (%) | 59 | 47 | 41 | 60 | 47 | 41 | 2.0 | 1.0 |
| SD | 3.94 | 0.16 | 1.56 | 4.18 | 0.17 | 1.59 | 0.02 | 0.01 |
AUC, area under the concentration–time curve; [Cmax, peak plasma concentration; CV, coefficient of variance; SD, standard deviation; Tmax, time to reach peak plasma concentration