Table 4.
Summary of Plasma PK Parameters of Isavuconazole
| Atorvastatin | Digoxin | Metformin | Methotrexate | |||||
|---|---|---|---|---|---|---|---|---|
| Parametera | Isavuconazole Alone (n = 24) | Isavuconazole + Atorvastatin (n = 24) | Isavuconazole Alone (n = 21)b | Isavuconazole + Digoxin (n = 21)b | Isavuconazole Alone (n = 20)c | Isavuconazole + Metformin (n = 20)c | Isavuconazole Alone (n = 23)d | Isavuconazole + Methotrexate (n = 23)d |
| AUCτ, h·μg/mL | 77.3 (22.0) | 81.2 (22.3) | 101.8 (30.2) | 101.1 (29.5) | 105.7 (31.0) | 111.7 (33.7) | 99.4 (30.8) | 102.7 (29.5) |
| Cmax, μg/mL | 5.3 (1.2) | 5.5 (1.3) | 6.1 (1.7) | 6.2 (1.7) | 7.1 (2.2) | 7.2 (2.0) | 6.2 (1.5) | 6.4 (1.6) |
| tmax, hours | 3.0 (1.5‐4.0) | 2.5 (1.5‐4.0) | 3.0 (2.0‐4.1) | 3.0 (2.0‐5.0) | 3.0 (1.5‐4.0) | 2.8 (2.0‐4.0) | 3.0 (2.0‐4.0) | 3.0 (2.0‐4.0) |
AUC, area under the plasma concentration‐time curve; Cmax, maximum observed concentration; TEAE, treatment‐emergent adverse event; tmax, time to reach Cmax.
a
Values are expressed as arithmetic mean (standard deviation), except tmax, which is expressed as median (range).
b
Two subjects discontinued the study prior to day 18 due to TEAEs; 1 subject discontinued the study prior to day 18 due to prohibited use of a concomitant medication.
c
Two subjects discontinued due to a TEAE, and 1 subject withdrew consent prior to metformin and isavuconazole coadministration (day 8).
d
One person withdrew consent during isavuconazole administration (day 6).