Table 5.
Comparison of model-based PK parameters of rivaroxaban across study populations [population mean (% SE)]*
| Parameter | ACS | VTE (knee) | VTE (hip) | AF | DVT |
|---|---|---|---|---|---|
| KA (h−1) | 1.24 (3.28) | 1.20 (8.9)§ | 1.81 (8.3)§ | 1.16 (14.1) | 1.23 (5.0) |
| CL/F (l h−1) | 6.48 (2.21) | 6.13 (4.5)¶ | 7.3 (4.0)¶ | 6.1 (3.9) | 5.67 (3.7) |
| V/F (l) | 57.9 (1.16) | 55.7 (5.8) | 49.1 (4.3) | 79.7 (6.1) | 54.4 (3.8) |
| Age effect on CL/F (year−1) | −0.0112 (8.82) | NA* | −0.015 (12.7) | −0.01050 (26.3) | −0.00692 (14.6) |
| SCR effect on CL/F[(mg dl−1)−1] | −0.151 (20.3) | NA* | −0.21 (21.6) | −0.19400 (34.0) | −0.269 (18.2) |
| LBM effect on V/F (kg−1) | 0.00833 (13.1) | NA* | 0.018 (13.5) | 0.01180 (32.4) | 0.0082 (17.8) |
| Age effect on V/F (year−1) | −0.00707 (16.3) | NA* | NA | −0.00133 (187.2) | −0.00486 (20.8) |
| F† | 0.85 (8.91) | 0.847 (4.4) | 0.740 (4.5) | NA†† | 0.79 (4.20) |
| F‡ | 0.71 (11.2) | 0.609 (4.6) | 0.533 (5.0) | NA†† | 0.63 (4.00) |
Definitions of typical subject: ACS (age = 57 years; SCR = 0.95 mg dl−1; LBM = 61 kg); VTE knee (CRCL = 104 ml min−1; BSA = 1.95 m2); VTE hip (age = 65 years; SCR = 0.78 mg dl−1; LBM = 51 kg); AF (age = 65 years; SCR = 1.05 mg dl−1; LBM = 57 kg); DVT (age = 61 years; SCR = 0.94 mg dl−1; LBM = 56 kg).
For ACS, relative bioavailability of 5, 7.5 and 10 compared with 2.5 mg; for VTE (knee) and VTE (kip), relative bioavailability (F) of 5 and 10 compared with 2.5 mg; for DVT, relative bioavailability of 20 compared with 10 mg.
For ACS, relative bioavailability of 15 and 20 compared with 2.5 mg; for VTE (knee) and VTE (hip), relative bioavailability of 20 and 30 compared with 2.5 mg; and for DVT, relative bioavailability of 30 and 40 compared with 10 mg.
Estimate for the fast absorption population based on a mixture model of KA for the VTE (hip and knee) populations only.
CL/F estimate for study day > 3.
Different covariates were used in this model (creatinine clearance on CL/F and body surface area on V/F).
Only 20 mg studied. Abbreviations: LBM, lean body mass; NA, not applicable; SCR, serum creatinine; %SE, relative standard error (%).