Table 3.
Noncompartmental pharmacokinetic parameters
| Parameter |
MEDI-546 |
|||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 0.1 mg/kg single dose | 0.3 mg/kg single dose | 1.0 mg/kg single dose | 3.0 mg/kg single dose | 10.0 mg/kg single dose | 20.0 mg/kg single dose |
0.3 mg/kg/week multiple dose |
1.0 mg/kg/week multiple dose |
5.0 mg/kg/week multiple dose |
||||
| 1 st dose | 4 th dose | 1 st dose | 4 th dose | 1 st dose | 4 th dose | |||||||
| Number of subjects |
1 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
5 |
3 |
| Cmax, mean (SD), μg/mL |
1.97 (NA) |
6.69 (1.47) |
23.3 (2.22) |
72.4 (13.7) |
213 (44.0) |
394 (83.5) |
6.43 (0.470) |
6.32 (1.01) |
19.1 (7.80) |
35.8 (15.5) |
87.6 (19.3) |
135 (26.5) |
| AUCa, mean (SD), μg · day/mL |
2.45 (NA) |
12.4 (4.91) |
102 (14.1) |
497 (105) |
2610 (728) |
4870 (1750) |
NA |
10.7 (2.53) |
NA |
159 (68.9) |
NA |
849 (165) |
| CL, mean (SD), mL/kg/day |
40.8 (NA) |
27.4 (11.0) |
9.94 (1.44) |
6.26 (1.43) |
4.07 (1.13) |
4.67 (2.18) |
NA |
NA |
NA |
NA |
NA |
NA |
| t1/2, mean (SD), d | 0.84 (NA) | 1.24 (0.358) | 2.96 (0.593) | 4.07 (1.23) | 7.70 (2.26) | 11.8 (2.06) | NA | 1.06 (0.174) | NA | 4.94 (1.47) | NA | 6.28 (0.921) |
aAUCinf for single-dose groups and AUC0–7 for multiple-dose groups.
AUCinf area under the serum concentration-time curve from zero to infinity; AUC0–7, AUC from day 0 to day 7 post dose administration; CL, systemic clearance; Cmax, maximum serum concentration; d, days; NA, not available; SD, standard deviation; t1/2, serum elimination half-life.