Table 2.
Total and unbound plasma anticoagulant PK parameters on day 6: rivaroxaban
| PK parameter | Andexanet alfa dose | Placebo* (n = 15) | ||||
|---|---|---|---|---|---|---|
| Cohort 1 (210-mg bolus; n = 6) | Cohort 2 (420-mg bolus; n = 6) | Cohort 3 (600-mg bolus; n = 6) | Cohort 4 (720/4 × 60 min; n = 6) | Cohort 5 (800/8 × 120 min; n = 6) | ||
| Total rivaroxaban, mean ± SD | ||||||
| Cmax, ng/mL | 676 ± 77.9 | 915 ± 112 | 1170 ± 267 | 1110 ± 178 | 1380 ± 296 | 325 ± 76.6 |
| C3.03,† ng/mL | 662 ± 84.6 | 898 ± 126 | 1060 ± 344 | 1100 ± 167 | 1270 ± 288 | 271 ± 68.4 |
| Tmax,‡ h (range) | 3.1 (3.06, 3.30) | 3.2 (3.05, 3.38) | 3.2 (3.18, 4.04) | 3.2 (2.97, 3.28) | 3.3 (3.09, 4.36) | 3.5 (2.42, 5.61) |
| AUC0-24, ng • h/mL | 3050 ± 395 | 3030 ± 488 | 4040 ± 503 | 4760 ± 861 | 7100 ± 1180 | 2250 ± 412 |
| CL/F, L/h | 6.6 ± 0.81 | 6.7 ± 0.97 | 5.0 ± 0.60 | 4.3 ± 0.65 | 2. 9 ± 0.55 | 9.2 ± 1.60 |
| t1/2, h | 7.3 ± 1.43 | 5.8 ± 0.97 | 7.7 ± 2.96 | 9.7 ± 5.52 | 7.4 ± 1.50 | 7.3 ± 2.09 |
| Unbound rivaroxaban, mean ± SD | ||||||
| Pre–andexanet alfa/placebo | 23.1 ± 5.59 | 20.9 ± 7.13 | 20.2 ± 9.83 | 22.1 ± 7.38 | 24.2 ± 8.50 | 21.8 ± 6.59 |
| C3.03,† ng/mL | 14.5 ± 3.06 | 9.42 ± 2.91 | 6.02 ± 5.25 | 7.3 ± 5.68 | 5.1 ± 3.32 | 24.3 ± 5.88 |
AUC, area under the plasma concentration–time curve from 0 to 24 hours; Cmax, maximum plasma concentration; C3.03, concentration at 3.03 hours postdose; CL/F, total clearance after oral administration; Tmax, time to maximum plasma concentration.
*
Pooled placebo from cohorts 1 to 5.
†
Anticoagulant plasma concentration measured 2 minutes after the end of the andexanet alfa bolus dose (3.03 hours after rivaroxaban dose).
‡
Median (minimum, maximum); time relative to rivaroxaban dose, τ = 24 hours.