Table 3.
Pharmacokinetic parameters of canagliflozin, M5, and M7 following single-dose administration of canagliflozin
| Parameter | Canagliflozin 100 mg | Canagliflozin 200 mg | ||||
|---|---|---|---|---|---|---|
| Normal renal function or mild renal impairment (n = 12) | Moderate renal impairment (n = 12) | Ratio (90 % CI) | Normal renal function or mild renal impairment (n = 12) | Moderate renal impairment (n = 12) | Ratio (90 % CI) | |
| Canagliflozin | ||||||
| C max (ng/mL) | 1,213.66 (337.87) | 1,197.13 (310.56) | 0.982 (0.821–1.173) | 2,415.61 (739.88) | 2,333.36 (414.90) | 0.989 (0.827–1.182) |
| AUC∞ (ng·h/mL) | 6,929 (1734) | 8,766 (2551) | 1.258 (1.061–1.490) | 14,815 (4162) | 17,835 (4434) | 1.216 (1.026–1.441) |
| t max (h) | 1.0 (1.0–3.0) | 1.0 (1.0–3.0) | 1.0 (1.0–6.0) | 1.0 (1.0–2.0) | ||
| t ½ (h) | 12.58 (3.14) | 15.50 (4.35) | 12.10 (2.66) | 15.15 (6.68) | ||
| CL/F (L/h) | 15.24 (3.65) | 12.15 (2.87) | 14.43 (3.73) | 11.73 (2.36) | ||
| Vd/F (L) | 269 (66) | 264 (81) | 244 (53) | 242 (67) | ||
| CLR (L/h) | 0.085 (0.037) | 0.064 (0.021) | 0.080 (0.029) | 0.058 (0.022) | ||
| Ae0–72h% | 0.541 (0.168) | 0.538 (0.229) | 0.559 (0.182) | 0.480 (0.143) | ||
| M5 | ||||||
| C max (ng/mL) | 546.50 (153.46) | 630.42 (180.80) | 1.148 (0.945–1.395) | 1,032.92 (247.63) | 1,267.33 (365.18) | 1.218 (1.002–1.479) |
| AUC∞ (ng·h/mL) | 6,454 (2047) | 11,132 (4798) | 1.655 (1.312–2.087) | 13,487 (4124) | 22,729 (8912) | 1.639 (1.299–2.067) |
| t max (h) | 2.0 (1.5–4.0) | 2.0 (1.5–4.0) | 2.0 (1.5–6.0) | 2.0 (1.5–4.0) | ||
| t ½ (h) | 12.28 (2.42) | 14.79 (4.44) | 12.33 (2.32) | 14.63 (5.45) | ||
| M7 | ||||||
| C max (ng/mL) | 1,092.08 (333.58) | 1,461.67 (565.50) | 1.306 (1.064–1.603) | 2,040.00 (780.85) | 2,715.83 (898.30) | 1.342 (1.093–1.646) |
| AUC∞ (ng·h/mL) | 10,152 (3659) | 18,205 (9025) | 1.709 (1.375–2.124) | 20,307 (8333) | 33,927 (13,214) | 1.669 (1.343–2.074) |
| t max (h) | 2.0 (2.0–4.0) | 2.0 (2.0–4.0) | 2.0 (1.5–6.0) | 2.0 (2.0–4.0) | ||
| t ½ (h) | 12.13 (2.74) | 15.62 (4.35) | 12.07 (2.21) | 15.26 (6.57) | ||
All results are presented as means (standard deviation) except t max, which is presented as the median (range). Ratio (90 % CI) represents the ratio of least square means of moderate renal impairment relative to normal renal function or mild renal impairment
Ae 0–72h % cumulative urinary excretion rate from time zero to 72 h, AUC ∞ area under the concentration–time curve from time zero to infinity, CI confidence interval, CL/F apparent total clearance, CL R renal clearance, C max maximum concentration, t ½ half-life, t max time to maximum concentration, V d /F apparent distribution volume at elimination phase