Table 2. Pharmacokinetic parameters of canagliflozin, M7, and M5 after administration of canagliflozin alone or with rifampin in healthy participants.
| Canagliflozin (300 mg q.d.) and rifampin (600 mg q.d.) | |||||
|---|---|---|---|---|---|
| Canagliflozin | |||||
| Parameter | Arithmetic mean (SD) | Geometric meana | |||
| Canagliflozin alone (n = 14) | Canagliflozin + rifampin (n = 14) | Canagliflozin alone (reference) (n = 14) | Canagliflozin + rifampin (test) (n = 14) | Estimated ratio (test/reference), % (90% CI) | |
| Cmax (ng/mL) | 2,474 (805) | 1,732 (385) | 2,358.29 | 1,692.05 | 71.75 (61.13; 84.21) |
| AUC∞ (ng×h/mL) | 21,695 (6151) | 10,489 (2535) | 20,938.95 | 10,210.73 | 48.76 (43.69; 54.43) |
| tmax (h)b | 2.00 (1.00 – 4.00) | 1.79 (1.00 – 4.00) | – | – | – |
| t1/2 (h) | 12.9 (2.42) | 11.2 (3.22) | – | – | – |
| Ae (% dose) | 0.578 (0.180) | 0.257 (0.127) | – | – | – |
| CLR (L/h) | 0.0849 (0.0318) | 0.0791 (0.0477) | – | – | – |
| M7 | |||||
| Cmax (ng/mL) | 1,905 (943) | 2340 (631) | 1,722.15 | 2,258.19 | 131.13 (115.45; 148.93) |
| AUC∞ (ng×h/mL) | 20,771 (10,728) | 13,390 (4,560)c | 18,820.25c | 12,716.53c | 67.57 (60.52; 75.44) |
| tmax (h)b | 3.50 (2.00 – 6.00) | 3.00 (2.00 – 4.00) | – | – | – |
| t1/2 (h) | 13.3 (2.65) | 10.7 (5.23)c | – | – | – |
| % Ae (dose) | 20.1 (5.72) | 12.8 (2.75) | – | – | – |
| CLR (L/h) | 4.62 (1.62) | 4.33 (1.50) | – | – | – |
| M/P Cmax ratio | 0.556 (0.170) | 1.02 (0.328) | – | – | – |
| M/P AUC∞ ratio | 0.687 (0.233) | 0.950 (0.319)c | – | – | – |
| M5 | |||||
| Cmax (ng/mL) | 2,420 (1196) | 3,616 (1095) | 2,161.41 | 3,473.25 | 160.69 (134.22; 192.38) |
| AUC∞ (ng×h/mL) | 21,903 (9556) | 23,122 (8944)c | 20,671.19c | 21,522.27c | 104.12 (92.83; 116.78) |
| tmax (h)b | 4.00 (3.00 – 10.00) | 4.00 (2.00 – 4.00) | – | – | – |
| t1/2 (h) | 12.4 (2.43) | 13.1 (3.12)c | – | – | – |
| % Ae (dose) | 9.23 (3.41) | 8.67 (2.79) | – | – | – |
| CLR (L/h) | 1.87 (0.559) | 1.73 (0.589) | – | – | – |
| M/P Cmax ratio | 0.707 (0.240) | 1.55 (0.413) | – | – | – |
| M/P AUC∞ ratio | 0.733 (0.233) | 1.58 (0.502)c | – | – | – |
%Ae = cumulative amount excreted into the urine, calculated as (Ae/dose)×100, and corrected for molecular weight for M7 and M5; AUC∞ = area under the plasma concentration-time curve from time 0 to infinite time; Cmax = maximum observed plasma concentration; CI = confidence interval; CLR = renal clearance, calculated as: Ae0–72/AUC0–72h; M/P AUC∞ Ratio = metabolite-to-parent ratio for AUC∞; M/P Cmax Ratio = metabolite-to-parent ratio for Cmax; q.d. = once daily; SD = standard deviation; t1/2 = elimination half-life; tmax = time to reach the maximum observed plasma concentration. aData analyzed on a logarithmic scale, but results transformed back to original scale; brepresented as median (range); cn = 13.