Summary of key plasma ADAMTS-13 FRETS-VWF73 PK parameters in adults
| Pharmacokinetic parameters . | Median (range) . | ||
|---|---|---|---|
| 5 U/kg (n = 3) . | 20 U/kg (n = 3) . | 40 U/kg (n = 7) . | |
| FRETS-VWF73 | |||
| IR, U/mL*kg/U | 0.0154 (0.0125-0.0187) | 0.0181 (0.0153-0.0290) | 0.0228 (0.0185-0.0290) |
| Cmax, U/mL | 0.075 (0.065-0.100) | 0.361 (0.300-0.583) | 0.941 (0.737-1.158) |
| tmax, h* | 1.00 (0.52-1.00) | 0.33 (0.25-0.53) | 0.37 (0.22-0.58) |
| AUC(0-inf), U*h/mL | ND† | 18.1 (15.4-24.9) | 52.3 (41.3-85.4) |
| AUC(0-t), U*h/mL | 0.388 (0.0528-1.68) | 14.9 (11.5-21.1) | 46.5 (37.2-78.8) |
| t1/2, h | ND† | 36.5 (29.5-69.2) | 66.9 (44.1-77.8) |
| MRT(0-inf), h | ND† | 48.876 (43.55-93.87) | 92.468 (55.71-124.01) |
| Cl, mL/h | ND† | 64.8 (53.3-100) | 59.3 (44.4-115) |
| Vss, mL | ND† | 4900 (2820-5000) | 5250 (4100-6830) |
| Technozym | |||
| IR, U/mL*kg/U | 0.0170 (0.0160-0.0179) | 0.0157 (0.0136-0.0254) | 0.0212 (0.0144-0.0261) |
| Cmax, U/mL | 0.087 (0.083-0.091) | 0.308 (0.272-0.512) | 0.844 (0.574-1.039) |
| tmax, h* | 0.25 (0.25-0.52) | 0.55 (0.28-0.97) | 0.30 (0.25-0.58) |
| AUC(0-inf), U*h/mL | 6.68 (4.32-17.4) | 21.8 (18.3-25.8) | 45.6 (40.6-89.1) |
| AUC(0-t), U*h/mL | 6.39 (4.26-8.43) | 20.6 (15.9-25.4) | 43.8 (37.3-80.4) |
| t1/2, h | 66.2 (44.2-238) | 64.4 (46.9-69.8) | 62.6 (46.5-77.0) |
| MRT(0-inf), h | 90.401 (69.41-383.36) | 90.663 (65.38-114.38) | 78.382 (63.54-124.58) |
| Cl, mL/h | 51.8 (13.3-88.9) | 54.7 (44.1-96.8) | 68.4 (45.7-111) |
| Vss, mL | 5090 (4680-6170) | 6260 (4000-6330) | 6010 (3130-8700) |
| ADAMTS13 antigen | |||
| IR, µg/mL*kg/µg | 0.0176 (0.0171-0.0194) | 0.0220 (0.0180-0.0354) | 0.0247 (0.0205-0.0328) |
| Cmax, µg/mL | 0.066 (0.062-0.066) | 0.296 (0.238-0.480) | 0.655 (0.549-0.879) |
| tmax, h* | 0.25 (0.25-0.52) | 0.55 (0.53-0.97) | 0.30 (0.22-1.12) |
| AUC(0-inf), µg*h/mL | 4.14 (4.14-5.90) | 18.1 (16.8-20.2) | 33.4 (29.4-67.8) |
| AUC(0-t), µg*h/mL | 4.05 (3.59-4.49) | 16.4 (15.6-19.9) | 30.4 (28.3-61.0) |
| t1/2, h | 93.9 (56.2-122) | 48.0 (47.0-82.3) | 70.4 (50.9-86.3) |
| MRT(0-inf), h | 131.365 (75.45-192.16) | 67.210 (62.37-128.74) | 87.134 (68.83-125.51) |
| Cl, mL/h | 58.3 (27.3-64.8) | 40.1 (35.8-83.1) | 61.8 (41.9-116) |
| Vss, mL | 5240 (4400-8510) | 4610 (2690-5180) | 4760 (3650-8150) |
| Pharmacokinetic parameters . | Median (range) . | ||
|---|---|---|---|
| 5 U/kg (n = 3) . | 20 U/kg (n = 3) . | 40 U/kg (n = 7) . | |
| FRETS-VWF73 | |||
| IR, U/mL*kg/U | 0.0154 (0.0125-0.0187) | 0.0181 (0.0153-0.0290) | 0.0228 (0.0185-0.0290) |
| Cmax, U/mL | 0.075 (0.065-0.100) | 0.361 (0.300-0.583) | 0.941 (0.737-1.158) |
| tmax, h* | 1.00 (0.52-1.00) | 0.33 (0.25-0.53) | 0.37 (0.22-0.58) |
| AUC(0-inf), U*h/mL | ND† | 18.1 (15.4-24.9) | 52.3 (41.3-85.4) |
| AUC(0-t), U*h/mL | 0.388 (0.0528-1.68) | 14.9 (11.5-21.1) | 46.5 (37.2-78.8) |
| t1/2, h | ND† | 36.5 (29.5-69.2) | 66.9 (44.1-77.8) |
| MRT(0-inf), h | ND† | 48.876 (43.55-93.87) | 92.468 (55.71-124.01) |
| Cl, mL/h | ND† | 64.8 (53.3-100) | 59.3 (44.4-115) |
| Vss, mL | ND† | 4900 (2820-5000) | 5250 (4100-6830) |
| Technozym | |||
| IR, U/mL*kg/U | 0.0170 (0.0160-0.0179) | 0.0157 (0.0136-0.0254) | 0.0212 (0.0144-0.0261) |
| Cmax, U/mL | 0.087 (0.083-0.091) | 0.308 (0.272-0.512) | 0.844 (0.574-1.039) |
| tmax, h* | 0.25 (0.25-0.52) | 0.55 (0.28-0.97) | 0.30 (0.25-0.58) |
| AUC(0-inf), U*h/mL | 6.68 (4.32-17.4) | 21.8 (18.3-25.8) | 45.6 (40.6-89.1) |
| AUC(0-t), U*h/mL | 6.39 (4.26-8.43) | 20.6 (15.9-25.4) | 43.8 (37.3-80.4) |
| t1/2, h | 66.2 (44.2-238) | 64.4 (46.9-69.8) | 62.6 (46.5-77.0) |
| MRT(0-inf), h | 90.401 (69.41-383.36) | 90.663 (65.38-114.38) | 78.382 (63.54-124.58) |
| Cl, mL/h | 51.8 (13.3-88.9) | 54.7 (44.1-96.8) | 68.4 (45.7-111) |
| Vss, mL | 5090 (4680-6170) | 6260 (4000-6330) | 6010 (3130-8700) |
| ADAMTS13 antigen | |||
| IR, µg/mL*kg/µg | 0.0176 (0.0171-0.0194) | 0.0220 (0.0180-0.0354) | 0.0247 (0.0205-0.0328) |
| Cmax, µg/mL | 0.066 (0.062-0.066) | 0.296 (0.238-0.480) | 0.655 (0.549-0.879) |
| tmax, h* | 0.25 (0.25-0.52) | 0.55 (0.53-0.97) | 0.30 (0.22-1.12) |
| AUC(0-inf), µg*h/mL | 4.14 (4.14-5.90) | 18.1 (16.8-20.2) | 33.4 (29.4-67.8) |
| AUC(0-t), µg*h/mL | 4.05 (3.59-4.49) | 16.4 (15.6-19.9) | 30.4 (28.3-61.0) |
| t1/2, h | 93.9 (56.2-122) | 48.0 (47.0-82.3) | 70.4 (50.9-86.3) |
| MRT(0-inf), h | 131.365 (75.45-192.16) | 67.210 (62.37-128.74) | 87.134 (68.83-125.51) |
| Cl, mL/h | 58.3 (27.3-64.8) | 40.1 (35.8-83.1) | 61.8 (41.9-116) |
| Vss, mL | 5240 (4400-8510) | 4610 (2690-5180) | 4760 (3650-8150) |
AUC(0-inf), area under the plasma-time concentration curve from zero to infinity; AUC(0-t), area under the plasma-time concentration curve from zero to the last measured point; max, maximum; min, minimum; ND, not determined; tmax, minimum time to reach Cmax.
Median (min − max).
n = 1 for AUC(0-inf), t1/2, MRT(0-inf), Cl, and Vss.