Table 3.
Summary of PK analysis in patients with type 3 VWD
| Parameter | N* | Mean (SD) | ||
|---|---|---|---|---|
| Product | VWF:RCo | VWF:Ag | FVIII:C | |
| AUC0-∞ | ||||
| rVWF-rFVIII | 17 | 1459.0 (475.3) | 2278.8 (714.8) | 5343.5 (2519.9) |
| pdVWF-pdFVIII | 15 | 1164.6 (527.4) | 2254.6 (1065.3) | 3312.1 (1414.6) |
| Cmax | ||||
| rVWF-rFVIII | 17 | 79.0 (22.0) | 80.0 (13.7) | 94.8 (24.0) |
| pdVWF-pdFVIII | 15 | 88.5 (32.8) | 126.7 (32.3) | 70.7 (17.0) |
| Tmax | ||||
| rVWF-rFVIII | 17 | 0.8 (0.6) | 1.4 (2.0) | 15.7 (11.4) |
| pdVWF-pdFVIII | 15 | 0.6 (0.1) | 0.6 (0.1) | 8.8 (8.9) |
| IR (in vivo) | ||||
| rVWF-rFVIII | 17 | 1.7 (0.7) | 2.2 (0.7) | 2.3 (0.6) |
| pdVWF-pdFVIII | 15 | 1.6 (0.6) | 1.9 (0.4) | 2.9 (0.8) |
| MRT | ||||
| rVWF-rFVIII | 17 | 23.6 (9.7) | 33.4 (11.4) | 38.5 (13.0) |
| pdVWF-pdFVIII | 15 | 18.8 (6.1) | 22.1 (5.5) | 32.58 (7.58) |
| Noncompartmental half-life | ||||
| rVWF-rFVIII | 17 | 16.4 (6.7) | 23.2 (7.9) | 26.7 (9.0) |
| pdVWF-pdFVIII | 15 | 13.0 (4.2) | 15.3 (3.8) | 22.6 (5.3) |
| T1/2 | ||||
| rVWF-rFVIII | 16 | 16.3 (7.1) | 25.5 (6.7) | — |
| pdVWF-pdFVIII | 15 | 14.4 (6.7) | 17.9 (3.5) | — |
| Cl | ||||
| rVWF-rFVIII | 17 | 4.1 (3.1) | 2.2 (2.5) | 2.6 (7.5) |
| pdVWF-pdFVIII | 15 | 5.2 (1.5) | 3.4 (0.9) | 0.9 (0.4) |
| AUC per dose-kg | ||||
| rVWF-rFVIII | 17 | 31.3 (13.4) | 38.1 (15.4) | 126.7 (193.3) |
| pdVWF-pdFVIII | 15 | 20.5 (5.6) | 49.9 (17.6) | 27.1 (10.6) |
| Vss | ||||
| rVWF-rFVIII | 17 | 75.9 (22.0) | 55.4 (17.7) | 32.6 (9.7) |
| pdVWF-pdFVIII | 15 | 96.3 (35.4) | 71.3 (15.6) | 27.4 (8.4) |
| Dose-kg | ||||
| rVWF-rFVIII | 17 | 47.2 (7.5) | 60.2 (9.6) | 5.8 (17.7) |
| pdVWF-pdFVIII | 15 | 56.4 (18.6) | 46.6 (19.3) | 125.6 (49.0) |
Subjects were treated in random order with a single 50 IU of VWF:RCo/kg infusion each of rVWF-rFVIII and pdVWF-pdFVIII with an 8-day washout period.
AUC0-∞, area under the plasma concentration curve from zero to infinity (h × U/dL); T1/2, half-life (hours); MRT, mean residence time (hours); Cl, clearance (mL/kg per hours); Vss, volume at a steady state (dL/kg); Cmax, maximum concentration (U/dL); Tmax, time to maximum concentration (hours); IR, incremental recovery ([U/dL]/[U VWF: RCo/kg] for VWF); ([U/dL]/[U FVIII: RCo/kg] for FVIII); AUC per dose/kg measured in h × U/dL/(U/kg); dose/kg in U/kg.
The PK analysis population consists of all subjects in the randomized crossover cohort who completed treatment with both the recombinant and plasma-derived products in the assigned order. Subjects with a nonneutralizing anti-VWF–binding antibody titer prior to rVWF-rFVIII treatment (subjects 5, 21, and 22) were excluded from the PK analysis.