There is also a marked discrepancy in PK between pdFIX and rFIX

There is also a marked discrepancy in PK between pdFIX and rFIX. Comparisons between the methodologically most robust studies on either species indicate that the average CL of recombinant FIX is twice as high as that of pdFIX [10]. This difference is confirmed in cross-over comparisons [37,38]. The typical elimination half-life of recombinant FIX is 17–23 h [9,37,39–41] as compared with approximately 30 h

for pdFIX [5,10,36]. The difference in CL between rFIX and pdFIX Cilomilast mw appears to be greater and more consistent between studies, than the difference in half-life, which demonstrate that the comparison cannot be based on only a single PK parameter. These differences heavily influence calculated dose requirements for prophylaxis. The median dose to maintain a 1.5 IU dL−1 trough level of pdFIX in eight adult patients was 1000 IU every third day or 500 IU alternate days [8]. As re-calculated from [9] the average doses of rFIX would be about 3800 IU every third

day and 1250 IU alternate days – an approximately threefold difference over all. In fair agreement with these separate estimations, the two cross-over studies [37,38] demonstrated that FIX plasma levels selleck chemical 48 h after a dose of rFIX were only approximately 50–70% of those obtained with the same dose of pdFIX. This can be directly translated to a 1.5- to 2-fold increase in dose requirement during prophylactic treatment. There are potentially significant clinical implications of the findings related above on the prescription of prophylactic regimens. There is very strong evidence to support the use of prophylaxis in children and this should be the recommended standard of care for all patients. Prophylaxis in adults is becoming more common. The observed difference

in FVIII half-life between adults Cyclooxygenase (COX) and children suggests that if similar trough levels are required in each age group, then widely different amounts of concentrate kg−1 would be required. For example, if alternate day dosing is used, the average young child would require 25 IU kg−1, whereas the average adult would require 12 IU kg−1, about half as much. The predicted dose in the average child is therefore the same as the standard Swedish dose used in many regimens [24,29] and the dose that has been shown to reduce bleeds and image-documented arthropathy significantly in young children receiving primary prophylaxis [27]. The simulations demonstrate that adults and adolescents require less FVIII kg−1 to maintain a desired trough level compared with young children. The groups, however, cannot be directly compared because adults are more likely to have arthropathy and to be receiving secondary prophylaxis, while adolescents are more likely to be participating in sporting activities. It is, therefore, not necessarily the case that the same trough levels are clinically appropriate for young children or active teenagers on primary prophylaxis and adults on secondary prophylaxis.

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