Table 3.
Pharmacokinetic parameter of rivaroxaban after a single oral 25 µg dose and during treatment with different azole fungistatic drugs in 12 healthy volunteers
| Rivaroxaban | Baseline | Itraconazole | Voriconazole | Fluconazole | Ketoconazole | Posaconazole | Isavuconazole |
|---|---|---|---|---|---|---|---|
| Cmax [pg/mL] | 822 (711– 952) | 1093* (927–1290) | 902ns (753–1081) | 972ns (828–1141) | 1388* (1182–1631) | 1146* (967–1358) | 871ns (741–1023) |
| AUC∞ [ng/mL min] | 218 (180–264) | 321* (268–385) | 254* (210–306) | 277* (241–318) | 506* (425–604) | 299* (247–362) | 247ns (209–293) |
| CL/F [mL/min] | 115 (94.7–139) | 77.8* (65.0–93.1) | 98.5* (81.5–119) | 90.3* (78.7–104) | 49.4* (41.4–58.9) | 83.5* (69.1–101) | 101ns (85.5–120) |
| Ae [% of dose] | 38.7 (30.4–49.4) | 50.0* (43.9–56.8) | 39.7ns (33.1–47.6) | 43.5ns (38.6–49.1) | 46.6* (38.8–55.9) | 51.5* (44.5–59.5) | 36.3ns (28.6–46.0) |
| CLrenal [mL/min] | 45.5 (31.0–66.9) | 40.0ns (32.5–49.4) | 40.4ns (30.5–53.6) | 40.4ns (33.9–48.1) | 24.3* (18.4–32.1) | 44.4ns (35.1–56.1) | 37.3ns (29.0–47.9) |
| CLnonrenal [mL/min] | 65.5 (54.6–78.6) | 36.4* (28.8–46.0) | 56.0ns (45.1–69.5) | 48.7* (40.7–58.3) | 23.9* (19.6–29.1) | 37.0* (28.6–47.9) | 60.9ns (48.8–76.0) |
| t½ [min] | 284 (237–341) | 302ns (269–339) | 287ns (232–355) | 271ns (246–299) | 346ns (295–406) | 282ns (231–343) | 254ns (224–290) |
| Vz/F [L] | 47.0 (38.9–56.8) | 33.9* (28.7–40.1) | 40.7ns (33.1–50.2) | 35.4* (31.1–40.2) | 24.7* (21.8–27.9) | 33.9* (28.5–40.4) | 37.1ns (32.4–42.5) |
| Vss/F [L] | 35.8 (31.0–41.4) | 26.6* (21.7–32.5) | 33.8ns (28.6–40.0) | 29.4* (25.9–33.5) | 22.2* (19.5–25.2) | 26.6* (22.2–32.0) | 31.3ns (27.6–35.5) |
| tmaxa [min] | 37.5 (30.0–90.0) | 45.0ns (30.0–90.0) | 45.0ns (30.0–90.0) | 37.5ns (30.0–120) | 30.0ns (15.0–150) | 30.0ns (30.0–75.0) | 45.0ns (30.0–120) |
Data are expressed as geometric mean (95% CI) unless otherwise specified
Test against baseline: ns
Ae amount excreted in urine as parent drug, AUC∞ area under the concentration–time curve extrapolated to infinity, CI confidence interval, CL/F apparent oral clearance, CLrenal renal clearance, CLnonrenal non-renal clearance, Cmax peak concentration, ns non-significant, tmax time to Cmax, t½ terminal elimination half-life, Vss/F volume of distribution at steady state, Vz/F apparent volume of distribution
*p < 0.05
aMedian and range