Pharmacokinetics of Optivate®, a high-purity concentrate of Factor VIII (FVIII) with von Willebrand factor (VWF), in patients with severe haemophilia A.

Anna Dmoszynska (1) , Andrzej Hellmann (2) , Trevor Baglin (3) , Denise O'Shaughnessy (4) , Jacek Treslinski (5) , Kazimierz Kuliczkowski (6) , Janusz Kloczko (7) , Charles Hay , Rukhsana Begum Shaikh-Zaidi (8) , Clive H Dash (9)

1 Klinika Hematologii
2 Klinika Hematologii
3 Haemophilia Centre
4 Haemophilia Centre
5 4. Klinika Haematologii
6 Klinika Haematologii
7 7. Klinika Haematologii
8 Medical dept.
9 Medical Department

Optivate® is a high purity FVIII/VWF concentrate, which is manufactured using two antiviral processes: solvent/detergent and terminal dry heating (800C for 72 hours). A multicentre, non-randomised open-label study in 15 patients was conducted to test the pharmacokinetics (PK) of Optivate®. PK variables were analysed for the patients' prior FVIII product (PK1), their first dose of Optivate® (PK2) and at 3 months therapy (PK3). Mean non compartmental half lives (h) were 14.1, 12.4 and 12.1 respectively (p = 0.45), mean clearances (mL/kg/h) were 3.6, 3.2 and 3.1 respectively (p= 0.051), MRTs (h) were 19.0, 17.3 and 17.4 respectively (p = 0.39) and mean AUC0 48 (h.IU/mL) were 14.3, 15.4 and 16.6 respectively (p=0.051) and mean AUC0 ∞ (h.IU/mL) were 15.9, 16.4 and 17.9 respectively (p = 0.18). The recovery data from this PK study was aggregated with recovery data collected from another study, with similar design but devoid of the other PK measurements. A total of 309 recoveries were conducted in 70 patients, The overall mean recovery per subject across 27 Optivate® batches was 2.7 IU/dL per IU/kg. There were no clinical differences between Optivate® and other FVIII products, and except for Vd, no statistically significant differences were seen with respect to any of the other PK variables, or in recovery between weeks 0 and 12. Therefore, the PK of FVIII is not affected by the processes used to manufacture Optivate®, which can be expected to be effective in the management of patients with haemophilia A.

Mots clés: Medicine

Anna Dmoszynska, Andrzej Hellmann, Trevor Baglin, Denise O'Shaughnessy, Jacek Treslinski, et al.. Pharmacokinetics of Optivate®, a high-purity concentrate of Factor VIII (FVIII) with von Willebrand factor (VWF), in patients with severe haemophilia A.. Haemophilia, 2010, 17 (2), pp.185. ⟨10.1111/j.1365-2516.2010.02414.x⟩. ⟨hal-00599533⟩