title: Recombinant full-length factor VIII (FVIII) and extended half-life FVIII products in prophylaxis--new insight provided by pharmacokinetic modelling.
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.
authors: Baxter Innovations GmbH, Vienna, Austria.
authors: A
authors: A
authors: Gringeri
authors: Baxter Innovations GmbH, Vienna, Austria.
authors: M
authors: M
authors: Wolfsegger
authors: Baxter Innovations GmbH, Vienna, Austria.
authors: K N
authors: KN
authors: Steinitz
authors: Baxter Innovations GmbH, Vienna, Austria.
authors: A J
authors: AJ
authors: Reininger
mesh_terms: D000293:Adolescent; D000328:Adult; D001777:Blood Coagulation; D001835:Body Weight; D002648:Child; D005169:Factor VIII / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D006207:Half-Life; D006400:Hematocrit; D006467:Hemophilia A / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011292:Premedication; D011994:Recombinant Proteins; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D011994:Recombinant Proteins; D005169:Factor VIII
keywords: extended half-life; factor VIII; haemophilia; pharmacokinetics; prophylaxis; trough level
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