title: Head-to-head comparison of the pharmacokinetic profiles of a high-purity factor IX concentrate (AlphaNine®) and a recombinant factor IX (BeneFIX®) in patients with severe haemophilia B.
abstract: Head-on comparative studies of factor IX (FIX) concentrates performed under standardized conditions are rarely conducted regardless of being a valuable instrument guiding health care providers towards better informed and cost-effective decisions. This study is an extension of a multicentre study that assessed the efficacy, safety and pharmacokinetics (PK) of AlphaNine(®) in 25 previously treated patients with severe haemophilia B (FIX:C ≤ 2%). After a washout period ≥ 7 days following the last PK performed with AlphaNine(®) after a dose of 65-75 IU kg(-1) , an identical PK study was performed with BeneFIX(®) on 22 of the same patients. Venous blood samples for analysis were taken at baseline and at 0.25, 0.5, 1, 3, 6, 9, 24, 48, 72 and 74 h post infusion. The outcomes of the comparison of the PK parameters were as follows: Mean (± SD) in vivo recovery (IVR) was 1.3 ± 0.4 IU dL(-1) per IU kg(-1) for AlphaNine(®) and 1.0 ± 0.3 IU dL(-1) per IU kg(-1) for BeneFIX(®) (P < 0.01). Mean terminal half-life, mean residence time, area under the curve, clearance and volume of distribution of BeneFIX(®) were 36.0 ± 12.8 h, 39.3 ± 13.9 h, 1631 ± 467 IU h dL(-1) , 0.046 ± 0.01 dL kg(-1) min(-1) and 1.75 ± 0.52 mL kg(-1) respectively. These values were not significantly different to those observed in AlphaNine(®), although BeneFIX(®) displayed higher than expected IVR values and lower than expected clearance values. In conclusion, AlphaNine(®) showed a comparable half-life, but an IVR significantly higher than that of BeneFIX(®). This dissimilarity may have implications on dosing requirements for on-demand treatment regimes affecting optimal resource allocation.
authors: National Center of Hematology, Sofia, Bulgaria. t.lissitchkov@yahoo.com
authors: T
authors: T
authors: Lissitchkov
authors: M
authors: M
authors: Matysiak
authors: K
authors: K
authors: Zavilska
authors: P
authors: P
authors: Laguna
authors: L
authors: L
authors: Gercheva
authors: A
authors: A
authors: Antonov
authors: A
authors: A
authors: Moret
authors: P
authors: P
authors: Caunedo
authors: J A
authors: JA
authors: Aznar
authors: M K
authors: MK
authors: Woodward
authors: A
authors: A
authors: Páez
mesh_terms: D000293:Adolescent; D000328:Adult; D054316:Biomarkers, Pharmacological; D005164:Factor IX / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D002836:Hemophilia B / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D008297:Male; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D054316:Biomarkers, Pharmacological; D011994:Recombinant Proteins; D005164:Factor IX
keywords: AlphaNine®; BeneFIX®; haemophilia B; pharmacokinetics; recombinant factor IX