Table 1.
Noncompartmental AZD6738 PK parameters
| Route Dose (mg/kg) | IV 10 | PO 2.0 | PO 7.5 | PO 20 | PO 75 | p-valueb | PO-extf 75 |
|---|---|---|---|---|---|---|---|
| Actual dose (mg/kg) | 11.7 | 1.92 | 8.8 | 23.4 | 90.5 | 88.4 | |
|
| |||||||
| Cmax (μg/mL) | 7.04 (0.93) | 0.160 (0.069) | 1.46 (0.26) | 4.96 (1.50) | 12.0 (1.0) | 14.1 (1.7) | |
| Cmax/dosea | 0.604 (0.093) | 0.0829 (0.034) | 0.172 (0.035) | 0.212 (0.075) | 0.133 (0.013) | 0.0395 | 0.160 (0.019) |
| Tmax (min) | 5 | 60 | 15 | 15 | 15 | 15 | |
| AUC0-360 (μg/mL•min) | 330 (17) | 22.8 (3.3) | 130 (18) | 545 (81) | 2,241 (135) | 0.0002 | 2,371 (185) |
| AUC0-360/dosea,c | 28.3 (1.5) | 11.8 (1.7) | 15.4 (2.1) | 23.3 (3.5) | 24.8 (1.5) | 26.8 (2.1) | |
| AUC0-∞ (μg/mL•min) | 337 | 25.4 | 144 | 578 | 2,495 | 2,371 (185) | |
| AUC0-∞ /dosea | 28.9 | 13.2 | 17.0 | 24.7 | 27.6 | 0.0002 | 26.8 (2.1) |
| Fd | - | 0.457 | 0.588 | 0.855 | 0.952 | ||
| CI (mL/min/kg)e | 34.5 | 75.7 | 58.8 | 40.4 | 36.3 | 37.3 | |
| Vd (L/kg)e | 4.92 | 11.4 | 11.0 | 5.50 | 6.06 | 5.66 | |
| Half-life (min) | 98.6 | 104 | 130 | 94.4 | 116 | 105 | |
| 0-24h urine (% dose) | 1.91 | 2.51 | 3.07 | 3.61 | 3.06 | 3.19 | |
| CIR (mL/min/kg) | 0.661 | 1.97 | 1.88 | 1.53 | 1.14 | 1.19 | |
| 0-24h feces (% dose) | 13.9 | 15.7 | 13.5 | 16.1 | 9.22 | 8.58 | |
Values represent the mean and error (SD for Cmax, SEM for AUC)
a:
calculated using exact dose
b:
ANOVA test of PO routes only
c:
% extrapolated ranges from 0.008 to 10.4%
d:
Based on AUC0-∞
e:
Apparent parameter for initial 4 PO doses 2, 7.5, 20, and 75 mg/kg
f:
Plasma PK parameters for the tissue distribution study