Table 3.
Pharmacokinetic parameters of enzalutamide in castration-resistant prostate cancer patients after a single oral dose
| Study | Dose (mg) | Subjects (n) | C max (μg/mL)a | t max (h)b | AUC24 (μg·h/mL)a | AUC∞ (μg·h/mL)a | t ½ (days)a | CL/F (L/h)a | V z/F (L)a |
|---|---|---|---|---|---|---|---|---|---|
| Dose escalationc | 30 | 3 | 0.4 ± 0.1 | 2.0 [0.4–4.0] | 5.5 ± 0.7 | 54 ± 21 | 6.9 ± 2.9 | 0.61 ± 0.22 | 133 ± 20 |
| 60 | 3 | 1.7 ± 0.5 | 0.5 [0.5–1.0] | 15.6 ± 0.5 | 94 ± 17 | 4.2 ± 1.3 | 0.66 ± 0.13 | 91 ± 14 | |
| 150 | 3 | 3.4 ± 0.8 | 0.5 [0.5–2.0] | 38.9 ± 8.4 | 334 ± 50 | 6.0 ± 1.5 | 0.46 ± 0.06 | 92 ± 12 | |
| 240 | 3 | 5.3 ± 0.9 | 1.0 [0.6–1.0] | 62.1 ± 23.9 | 474 ± 138 | 5.8 ± 0.9 | 0.54 ± 0.18 | 112 ± 56 | |
| 360 | 6 | 7.1 ± 2.5 | 1.0 [0.5–2.2] | 80.5 ± 14.9 | 715 ± 122 | 6.2 ± 1.1 | 0.52 ± 0.09 | 109 ± 18 | |
| 480d | 6 | 6.8 ± 3.5 | 1.5 [0.5–2.1] | ND | 1010 ± 378 | 6.0 ± 2.9 | 0.54 ± 0.23 | 101 ± 30 | |
| 600d | 3 | 5.2 ± 1.0 | 1.0 [1.0–2.0] | ND | 896 ± 270 | 5.4 ± 1.6 | 0.72 ± 0.26 | 127 ± 11 | |
| All doses combined | 27 | NC | 1.0 [0.4–4.0] | NC | NC | 5.8 ± 1.6 | 0.56 ± 0.17 | 110 ± 32 | |
AUC ∞ area under the plasma concentration–time curve from time zero to infinity, AUC 24 area under the plasma concentration–time curve from time zero to 24 h after administration of a single dose, CL/F apparent oral clearance, C max maximum plasma concentration, NC not calculated, ND not determined, t ½ half-life, t max time to reach Cmax, V z /F apparent volume of distribution during the terminal phase
aValues are expressed as mean ± standard deviation
bValues are expressed as median [range]
cDose-escalation study, single-dose period [5]
d480 and 600 mg were administered as a divided dose (240 and 300 mg twice daily, respectively), with approximately 12 h between the two doses