TABLE 2.
Geometric mean values of dabigatran pharmacokinetic parameters in arm B (COBI)a
| Pharmacokinetic parameter | AUC0–24 (ng · h/ml) | AUC0–∞ (ng · h/ml) | Cmax (ng/ml) | Tmax (h) | CL/F (liters/hr) | V/F (liters) | t1/2 (h) | kel (1/h) |
|---|---|---|---|---|---|---|---|---|
| Geometric mean value (% CV) | ||||||||
| Phase 1 (DE alone) | 959.49 (63.71) | 1,046.94 (66.55) | 129.74 (61.49) | 3.09 (32.51) | 143.28 (50.61) | 130.00 (45.69) | 6.29 (18.68) | 0.11 (15.95) |
| Phase 2 (DE + COBI separated) | 2051.98 (61.46) | 2,193.93 (60.87) | 258.14 (51.66) | 3.74 (30.25) | 68.37 (48.51) | 57.45 (47.77) | 5.82 (11.76) | 0.12 (11.26) |
| Phase 3 (DE + COBI simultaneously) | 2303.39 (40.37) | 2,483.26 (40.83) | 302.40 (44.47) | 3.20 (18.04) | 60.40 (57.69) | 51.61 (43.71) | 5.92 (15.54) | 0.12 (15.69) |
| GMR (90% CI) for comparison of phases | ||||||||
| Phase 2 vs phase 1 | 2.14 (1.65–2.63)b | 2.10 (1.65–2.54)b | 1.99 (1.42–2.56)b | 1.21 (1.00–1.42) | 0.48 (0.39–0.56)b | 0.44 (0.35–0.53)b | 0.93 (0.88–0.98)c | 1.08 (1.01–1.14)c |
| Phase 3 vs phase 1 | 2.31 (1.83–2.78)b | 2.27 (1.81–2.73)b | 2.27 (1.59–2.96)b | 1.03 (0.88–1.18) | 0.44 (0.37–0.51)b | 0.41 (0.34–0.48)b | 0.92 (0.88–0.97)c | 1.08 (1.03–1.16)c |
a
AUC0–24, area under the concentration-versus-time curve from time zero to 24 h; AUC0-∞, area under the concentration-versus-time curve from time zero to infinity; Cmax, maximum plasma concentration; Tmax, time to reach the maximum plasma concentration; CL/F, apparent oral clearance; V/F, apparent oral volume of distribution; t1/2, plasma half-life; kel, elimination rate constant; DE, dabigatran etexilate; COBI, cobicistat; CV, coefficient of variation; CI, confidence interval.
b
P < 0.001, based on a paired Student t test.
c
P < 0.05, based on a paired Student t test.