Table 3. Summary of mean PK parameters of PRS-050 by dosing cohort.
|
PRS-050 dose (mg/kg)
|
|||||||
|---|---|---|---|---|---|---|---|
|
Parameter* |
0.1 (n=3) | 0.5 (n=4) | 1.5 (n=6) | 3.0 (n=3) | 6.0 (n=3) | 10.0 (n=6) | |
| After a single IV administration | |||||||
| AUC0-last, μg.h/mL | 184 (119) | 1980 (25.5) | 4370 (39.7) | 11,800 (34.6) | 26,900 (44.8) | 34,500 (33.5) | |
| AUC0-∞, μg.h/Ml | 227 (83.9) | 2160 (24.5) | 4880 (39.1) | 14,300 (46.3) | 31,200 (50.1) | 38,100 (33.6) | |
| Cmax, μg/mL | 4.2 (34.3) | 22.9 (21.0) | 49.1 (17.7) | 102.0 (56.6) | 214.0 (49.7) | 327.0 (51.1) | |
| C’168h, μg/mL | 0.3 (273) | 4.8 (26.0) | 10.4 (38.3) | 28.9 (58.8) | 63.5 (42.9) | 79.2 (38.0) | |
| Tmax, h | 0.32 (0.27–0.55) | 0.31 (0.27–0.35) | 0.31 (0.25–0.55) | 0.25 (0.25–0.37) | 0.47 (0.33–0.48) | 0.52 (0.27–0.60) | |
| t1/2, days | 3.2 (87.0) | 5.5 (28.0) | 6.0 (15.5) | 6.8 (37.9) | 7.0 (19.8) | 6.3 (8.9) | |
| CL, mL/min/kg | 0.0073 (83.9) | 0.0039 (24.5) | 0.0051 (39.1) | 0.0035 (46.3) | 0.0032 (50.1) | 0.0044 (33.6) | |
| Vz, L/kg | 0.049 (16.8) | 0.044 (36.8) | 0.064 (29.6) | 0.049 (48.4) | 0.047 (37.1) | 0.057 (36.1) | |
| Vss, L/kg | 0.048 (15.8) | 0.044 (35.1) | 0.061 (28.7) | 0.050 (48.0) | 0.046 (38.1) | 0.055 (35.1) | |
| After repeated once weekly IV administration | |||||||
| Ctrough, ss, ng/mL | 900 (52.2) | 6910 (29.4) | 17,900 (72.2) | 44,900; 94,800† | 93,100 (76.6) | 107,000 (58.2) | |
| RACtrough | 2.67 (126) | 1.46 (30.7) | 1.46 (44.6)§ | 1.79, 1.82† | 1.47 (34.2) | 1.35 (59.3) | |
* Geometric mean values (coefficient of variation; CV%) presented except for Tmax where median (range) presented.
† n=2.
§ n=3.
AUC, area under the plasma-concentration versus time curve; CL, clearance; Cmax, maximum plasma concentration; Cmin, trough or minimum plasma concentration; IV, intravenous; PK, pharmacokinetic; RACtrough, accumulation ratio based on trough concentrations; t1/2, terminal half-life; Vss, volume of distribution at steady state; Vz, volume of distribution during the terminal phase.