Table 2.
Summary statistics for apixaban pharmacokinetics
| Pharmacokinetic parameter* | Ketoconazole DDI study | Diltiazem DDI study | ||||
|---|---|---|---|---|---|---|
| (n = 18) | (n = 18) | |||||
| Apixaban | Apixaban + ketoconazole | Point estimate of RGM (90% CI) | Apixaban | Apixaban + diltiazem | Point estimate of RGM (90% CI) | |
| Cmax (ng ml−1) | 139.5 (32) | 225.3 (36) | 1.62 (1.47, 1.78) | 148.1 (38) | 194.6 (41) | 1.31 (1.16, 1.49) |
| [80, 250] | [103, 391] | [76, 304] | [119, 463] | |||
| AUC(0,tlast) (ng ml−1 h) | 1490 (28) | 2939 (38) | 1.97 (1.80, 2.16) | 1779 (40) | 2475 (40) | 1.39 (1.24, 1.56) |
| [818, 2165] | [1288, 5612] | [892, 3574] | [1228, 5144] | |||
| AUC(0,∞) (ng ml−1 h) | 1523 (28) | 3027 (37) | 1.99 (1.81, 2.18) | 1897† (38) | 2606 (39) | 1.40 (1.23, 1.59) |
| [846, 2229] | [1306, 5859] | [941, 3589] | [1242, 5229] | |||
| tmax (h) | 4 (1, 4) | 4 (3, 4) | – | 3 (2, 8) | 4 (2, 4) | – |
| t1/2 (h) | 11.3 (5.8) | 13.8 (6.3) | – | 17.2† (7.4) | 16.3 (7.8) | – |
| [4.6, 25] | [5.6, 34] | [8.6, 30] | [5.6, 37] | |||
*
Geometric mean (%CV) [min, max] for Cmax, AUC(0,tlast) and AUC(0,∞); median (min,max) for tmax; arithmetic mean (SD) [min, max] for t1/2.
†
n = 17; in one subject AUC(0,∞) and t1/2 could not be calculated. AUC(0,tlast), area under concentration–time curve from time zero to last quantifiable concentration; AUC(0,∞), area under concentration–time curve from time zero to infinity; CI, confidence interval; Cmax, observed peak plasma concentration; CV, coefficient of variation; DDI, drug–drug interaction; RGM, ratio of geometric means estimated as concomitant treatment vs. apixaban alone; SD, standard deviation; t1/2, elimination half-life; tmax, time taken to reach Cmax.