We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Recombinant full-length factor VIII (FVIII) and extended half-life FVIII products in prophylaxis - new insight provided by pharmacokinetic modelling.
- Authors
Gringeri, A.; Wolfsegger, M.; Steinitz, K. N.; Reininger, A. J.
- Abstract
The pharmacokinetics ( PK) of extended half-life factor VIII (FVIII) products might allow longer dosing intervals in prophylaxis, potentially affecting its efficacy. We used published population PK models of a recombinant full-length FVIII (rAHF- PFM) and a recombinant B-domain-deleted FVIII Fc fusion product (rFVIIIFc) to assess the time spent weekly with FVIII levels below 3 IU dL−1 or above 10 IU dL−1. These FVIII levels were chosen based on the observation that trough levels of 1 IU dL−1 may not be sufficient in all patients. This approach was applied to a simulated population of 1000 severe haemophilia A subjects with dosing regimens included in the prescribing information or evaluated in clinical trials. FVIII levels remained ≥3 IU dL−1 in 57% of patients treated with rAHF- PFM 30 IU kg−1 every 48 h compared with 41.1%, 18.3%, 0.9% and 0% of patients treated with rFVIIIFc 30 IU kg−1 every 72 h, 50 IU kg−1 every 96 h or 120 h and 65 IU kg−1 every 168 h respectively. Patients on rAHF- PFM 30 IU kg−1 every 48 h spent more time weekly with FVIII levels above 10 IU dL−1 than those on rFVIIIFc 50 IU kg−1 every 96 h or 120 h, and 65 IU kg−1 every 168 h. In conclusion, PK modelling indicates that choice and dosing intervals of standard and extended half-life FVIII products require careful evaluation of individual PK to allow more time at protective levels, especially in patients with active lifestyles.
- Subjects
PHARMACOKINETICS; HALF-life (Biology); BLOOD coagulation; CLINICAL trials; RECOMBINANT DNA
- Publication
Haemophilia, 2015, Vol 21, Issue 3, p300
- ISSN
1351-8216
- Publication type
Article
- DOI
10.1111/hae.12605