Table 3. Pharmacokinetic parameters of canagliflozin, M7 and M5 after administration of canagliflozin alone or with probenecid in healthy participants.
| Canagliflozin (300 mg q.d.) and probenecid (500 mg b.i.d.) | |||||
|---|---|---|---|---|---|
| Canagliflozin | |||||
| Parameter | Arithmetic mean (SD) | Geometric meana | |||
| Canagliflozin alone (n = 12) | Canagliflozin + probenecid (n = 12) | Canagliflozin alone (reference)(n = 11) | Canagliflozin + probenecid (test) (n = 11) | Estimated ratio (test/reference), % (90% CI) | |
| Cmax.ss (ng/mL) | 2,699 (814) | 3,105 (680) | 2,653.85 | 3,008.66 | 113.37 (100.37; 128.06) |
| AUC∞.ss (ng×h/mL) | 21,861 (4290) | 26,225 (5261) | 21,543.95 | 26,011.71 | 120.74 (116.37; 125.27) |
| tmax.ss (h)b | 1.92 (1.42– 3.92) | 1.67 (1.42 – 5.92) | – | – | – |
| % Ae (dose) | 0.609 (0.217) | 0.495 (0.136) | – | – | – |
| CLR (L/h) | 0.0868 (0.0297) | 0.0569 (0.00944) | – | – | – |
| M7 | |||||
| Cmax.ss (ng/mL) | 1,676 (611) | 2,299 (811) | 1,644.65 | 2,114.68 | 128.58 (120.37; 137.35) |
| AUC∞.ss (ng×h/mL) | 16,480 (5661) | 22,405 (7746) | 16,143.27 | 21,004.83 | 130.12 (126.11; 134.25) |
| tmax.ss (h)b | 2.92 (1.92 – 3.92) | 2.92 (1.92 – 5.92) | – | – | – |
| % Ae (dose) | 21.2 (4.13) | 12.2 (2.40) | – | – | – |
| CLR (L/h) | 5.80 (1.91) | 2.46 (0.995) | – | – | – |
| M/P Cmax.ss ratio | 0.479 (0.190) | 0.564 (0.220) | – | – | – |
| M/P AUC∞.ss ratio | 0.579 (0.238) | 0.652 (0.249) | – | – | – |
| M5 | |||||
| Cmax.ss (ng/mL) | 2,448 (805) | 3,164 (934) | 2,363.34 | 3,059.42 | 129.45 (116.45; 143.91) |
| AUCτ.ss (ng×h/mL) | 20,789 (7928) | 30,607 (11801) | 19,743.25 | 28,890.54 | 146.33 (135.09; 158.50) |
| tmax.ss (h)b | 2.92 (2.92 – 3.92) | 3.92 (1.92 – 5.92) | – | – | – |
| % Ae (dose) | 11.2 (2.74) | 3.09 (0.943) | – | – | – |
| CLR (L/h) | 2.47 (0.709) | 0.454 (0.197) | – | – | – |
| M/P Cmax.ss ratio | 0.695 (0.249) | 0.765 (0.217) | – | – | – |
| M/P AUCτ.ss ratio | 0.714 (0.286) | 0.862 (0.284) | – | – | – |
%Ae = cumulative amount excreted into the urine, calculated as (Ae/dose)×100, and corrected for molecular weight when necessary; AUCτ.ss = area under the plasma concentration-time curve during a dosing interval at steady state; b.i.d. = twice daily; Cmax.ss = maximum observed plasma concentration during a dosing interval at steady state; CI: confidence interval; CLR = renal clearance, calculated as Ae24/AUC24; M/P AUCτ.ss ratio = metabolite-to-parent ratio for AUCτ.ss; M/P Cmax.ss ratio = metabolite-to-parent ratio for Cmax.ss; q.d. = once daily; SD = standard deviation; tmax.ss = time to reach the maximum observed plasma concentration during a dosing interval at steady state; τ = 24 hours interval. aData analyzed on a logarithmic scale, but results transformed back to original scale; brepresented as median (range).