Table 2.
Plasma Pharmacokinetics of Isavuconazole in the Presence and Absence of Rifampin and Ketoconazole
| Isavuconazole PK (± Rifampin) | Isavuconazole PK (± Ketoconazole) | |||
|---|---|---|---|---|
| Parametera | Isavuconazole Alone (n = 25)b | Isavuconazole + Rifampin (n = 24)c | Isavuconazole Alone (n = 12) | Isavuconazole + Ketoconazole (n = 12) |
| AUC0‐∞, h·μg/mL | 233.1 (122.9) | 5.8 (1.4) | 84.8 (22.2) | 466.4 (199.4) |
| AUClast, h·μg/mL | 206.0 (89.3) | 5.6 (1.4) | 64.9 (17.5) | 238.5 (45.4) |
| AUCτ, h·μg/mL | 38.0 (8.2) | 3.9 (0.8) | ND | ND |
| Cmax, μg/mL | 2.4 (0.5) | 0.6 (0.2) | 2.2 (0.5) | 2.4 (0.6) |
| tmax, hours | 2.0 (1.0−8.0) | 2.0 (1.0−4.0) | 2.0 (2.0−4.0) | 3.0 (2.0−4.0) |
| t½, hours | 83.6 (38.9) | 19.7 (4.9) | 117.0 (65.6) | 430.1 (198.0) |
| CL/F, L/h | 2.8 (0.6) | 27 (6.2) | 2.5 (0.6) | 0.5 (0.2) |
| Geometric Least‐Squares Mean Ratio, % (90% CI) | ||||
| AUC0‐∞ | 3 (2, 3) | 522 (409, 666) | ||
| AUClast | 3 (3, 3) | 373 (319, 435) | ||
| AUCτ | 10 (9, 11) | ND | ||
| Cmax | 25 (23, 27) | 109 (93, 127) | ||
AUC, area under the concentration–time curve; Cmax, maximum concentration; CL/F, clearance; CI, confidence interval; ND, not done; PK, pharmacokinetics; t½, half‐life; tmax, time to Cmax.
a
Values are expressed as arithmetic mean (standard deviation) except tmax, for which median (range) is provided.
b
One subject discontinued the study during isavuconazole‐alone administration (day 9).
c
Two subjects discontinued the study during isavuconazole‐alone administration (days 9 and 14).