TABLE 1.
Geometric mean values of dabigatran pharmacokinetic parameters in arm A (RTV)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) | 747.84 (48.77) | 814.87 (48.24) | 93.41 (44.22) | 3.35 (35.46) | 190.08 (39.13) | 159.11 (39.60) | 6.31 (9.20) | 0.11 (8.70) |
| Phase 2 (DE + RTV separated) | 528.13 (36.84) | 576.12 (37.60) | 68.08 (34.71) | 2.43 (25.30) | 260.36 (32.61) | 235.90 (36.76) | 6.56 (13.54) | 0.11 (13.96) |
| Phase 3 (DE + RTV simultaneously) | 832.10 (43.91) | 938.63 (41.60) | 105.65 (36.07) | 3.53 (39.84) | 159.81 (42.31) | 135.55 (40.13) | 6.14 (12.10) | 0.11 (14.01) |
| GMR (90% CI) for comparison of phases | ||||||||
| Phase 2 vs phase 1 | 0.71 (0.60–0.81)b | 0.71 (0.60–0.82)b | 0.73 (0.61–0.85)b | 0.73 (0.62–0.84)b | 1.37 (1.16–1.58)b | 1.48 (1.25–1.71)b | 1.04 (0.99–1.09) | 0.95 (0.90–1.01) |
| Phase 3 vs phase 1 | 1.11 (0.89–1.33) | 1.15 (0.93–1.37) | 1.13 (0.90–1.36) | 1.05 (0.80–1.30) | 0.84 (0.64–1.04) | 0.85 (0.68–1.03) | 0.97 (0.91–1.03) | 1.02 (0.95–1.09) |
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; RTV, ritonavir; CV, coefficient of variation; CI, confidence interval.
b
P < 0.05, based on a paired Student t test.