Summary of terminal half-lives of rFIXFc and rFIX after a single intravenous dose
| Species . | rFIX, h . | rFIXFc, h . |
|---|---|---|
| Normal mice | 12.3 | 47.2 ± 4.8 |
| FIX-deficient mice | 13.2 | 46.2 ± 10.1 (47) |
| FcRn/β2m KO mice | 16.5 ± 3.0 | 16.9 ± 2.1 |
| hFcRn/hβ2m transgenic Tg32b mice | 14.2 ± 2.9 | 53.0 ± 6.6 |
| Rats | 5.8 | 34.8 ± 5.3 |
| FIX-deficient dogs | (17-18)* | 47.5 (38.3) |
| Monkey | 12.7† | 47.3 ± 9.1 |
| Species . | rFIX, h . | rFIXFc, h . |
|---|---|---|
| Normal mice | 12.3 | 47.2 ± 4.8 |
| FIX-deficient mice | 13.2 | 46.2 ± 10.1 (47) |
| FcRn/β2m KO mice | 16.5 ± 3.0 | 16.9 ± 2.1 |
| hFcRn/hβ2m transgenic Tg32b mice | 14.2 ± 2.9 | 53.0 ± 6.6 |
| Rats | 5.8 | 34.8 ± 5.3 |
| FIX-deficient dogs | (17-18)* | 47.5 (38.3) |
| Monkey | 12.7† | 47.3 ± 9.1 |
Animals were administered a single dose of rFIXFc (∼ 200 IU/kg in normal mice [n = 8], FIX-deficient mice [n = 11], FcRn KO mice [n = 4], FcRn Tg32B mice [n = 4], and rats [n = 9]; 140 IU/kg for FIX-deficient dogs [n = 2]; and 25, 100, or 500 IU/kg for monkeys [n = 2, 3, or 3, respectively]) or rFIX (100 IU/kg in normal mice [n = 5] and FIX-deficient mice [n = 5] and 200 IU/kg in FcRn KO mice [n = 4], FcRn Tg32B mice [n = 4], and rats [n = 5]). Blood samples were collected at various time points between 0.25 hours and 168 hours and plasma prepared for analysis of protein concentration by rFIXFc or FIX-specific ELISA. Data were then analyzed using WinNonLin to generate terminal half-life, utilizing the best fit of data from all time points. FIX activity data was also obtained from FIX-deficient mice (n = 4 / time point) and FIX-deficient dogs (n = 2) and terminal half-life based on activity calculated (listed in parentheses).
Published values of t1/2 for recombinant FIX, based on activity data.22,23
Published values of t1/2 for recombinant FIX, based on ELISA data.23