Table 1.
Pharmacokinetic characteristics of various factor concentrates
| Single-arm studies | |||||
|---|---|---|---|---|---|
| Concentrate | Reference | Patient age (years) | t1/2 (mean ± SD, hours) | Cl (mean ± SD, dL h−1/kg−1) | Vss (mean ± SD, mL/kg−1) |
| Single-arm studies | |||||
| Plasma-derived FVIII | Wolf, 2004 | 11-16 | 11.8 ± 4.2 | 0.15 ± 0.05 | NA |
| Saez, 1999 | 18-44 | 12.5 ± 5.4 | 0.51 ± 0.03 | NA | |
| Powell, 2000 | 14-46 | 16.0 ± 3.1 | NA | NA | |
| Advate | Tarantino, 2004 | 10-65 | 11.2 ± 2.5 | 0.30 ± 0.01 | 46.0 ± 10.0 |
| Blanchette, 2004 | <6 | 9.7 ± 1.9 | 0.44 ± 0.01 | 51.4 ± 12.3 | |
| Valentino, 2012 | 7-59 | 13.9 ± 5.3 | 0.39 ± 0.01 | NA | |
| Malhangu, 2014 | ≥12 | 12.4 ± 2.0 | 0.30 ± 0.02 | NA | |
| Kogenate | Abshire, 2000 | 12-60 | 16.8 ± 4.7 | NA | NA |
| Rotschild, 2002 | 12-59 | 14.4 ± 2.7 | NA | NA | |
| ReFacto | Lusher, 2003 | NA | 14.5 ± 5.3 | NA | NA |
| Morfini, 2003* | ≥12 | 17.4 ± 13.0 | 0.38 ± 0.01 | 78.5 ± 25.6 | |
| Santoro, 2009* | 21-69 | 12.9 ± 4.7 | 0.50 ± 0.01 | 46.6 ± 12.1 | |
| Recht, 2009 | 12-60 | 11.2 ± 5.0 | 0.45 ± 0.02 | NA | |
| NovoEight | Jimenez-Yuste, 2015 | ≥12 | 11.2 ± 4.2 | 0.35 ± 0.01 | 46.7 ± 9.6 |
| N8-GP | Tiede, 2013 | 2-60 | 19.0 ± 5.5 | 0.18 ± 0.09 | 45.3 ± 17.8 |
| Eloctate | Malhangu, 2014 | ≥12 | 19.7 ± 2.3 | 0.20 ± 0.01 | NA |
| Crossover studies | |||||
| Monoclonate-P | Deitcher, 1999 | 27-41 | 15.5 ± 2.8 | 0.28 ± 0.06 | 77.1 ± 13.9 |
| Bioclate | 14.9 ± 2.9 | 0.40 ± 0.04 | 95.0 ± 21.9 | ||
| ReFacto | Kessler, 2005 | 18-44 | 14.8 ± 5.6 | NA | NA |
| Hemofil | 13.7 ± 3.7 | ||||
| ReFacto | Di Paola, 2007 | 19-72 | 13.0 ± 3.1 | 0.39 ± 0.14 | 58.6 ± 13.7 |
| Advate | 13.6 ± 3.8 | 0.40 ± 0.14 | 61.7 ± 18.6 | ||
| BAY 79-4980 | Powell, 2008 | 12-60 | 11.4 ± 2.5 | 0.31 ± 0.08 | 50.0 ± 9.5 |
| Recombinate | 11.6 ± 2.5 | 0.31 ± 0.07 | 49.4 ± 9.6 | ||
| N8 | Martinowitz, 2011 | 13-54 | 10.8 ± 4.9 | 0.41 ± 0.11 | 59.8 ± 11.7 |
| Advate | 11.1 ± 3.5 | 0.42 ± 0.12 | 61.3 ± 7.9 | ||
| Benefix | Negrier, 2011 | NA | 19.3 | 0.69 | 194.98 |
| N9-GP | 96.2 | 0.07 | 99.5 | ||
| Plasma derived | 17.8 | 0.55 | 140.58 | ||
| BeneFIX | Santagostino, 2012 | 15-58 | 17.2 ± 2.3 | 0.05 ± 0.01 | 132.5 ± 34.1 |
| F9-fusion protein | 91.6 ± 20.7 | 0.05 ± 0.001 | 99.1 ± 15.5 | ||
| Plasma derived | 14.6 ± 1.7 | 0.007 ± 0.002 | 91.6 ± 15.0 | ||
| BeneFIX | Powell, 2013 | 12-71 | 33.8 ± 2.4 | 0.06 ± 0.004 | 261.1 ± 19.5 |
| Alprolix | 82.1 ± 5.5 | 0.03 ± 0.002 | 314.8 ± 18.8 | ||
| Alphanine | Lissitchov, 2013 | 15-45 | 32.7 ± 7.4 | 0.04 ± 0.001 | 134.0 ± 42.0 |
| BeneFIX | 36.0 ± 12.8 | 0.05 ± 0.001 | 175.0 ± 52.0 | ||
The table shows PK parameters reported in selected studies. Variability across concentrates can be appraised by comparing values across different rows, whereas the variability among patients is represented by the standard deviations on each of the row. An approximate estimate of the lowest and highest value found in 95% of the population can be calculated as mean minus twice the SD or mean plus twice the SD, respectively. For the half-life of Advate in the Tarantino study, for example, half-life would go from 6.2 to 16.2 hours.
Cl, clearance; NA, not available; t1/2, terminal half-life; SD, standard deviation; Vss, plasma volume at the steady state.
1 stage clotting test, generic standard.