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Pharmacokinetics of plasma‐derived vs. recombinant FVIII concentrates: a comparative study
Author(s) -
Morfini M.,
Marchesini E.,
Paladino E.,
Santoro C.,
Za E.,
Iorio A.
Publication year - 2015
Publication title -
haemophilia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.213
H-Index - 92
eISSN - 1365-2516
pISSN - 1351-8216
DOI - 10.1111/hae.12550
Subject(s) - pharmacokinetics , haemophilia a , bioequivalence , medicine , haemophilia , recombinant dna , pharmacology , distribution (mathematics) , plasma concentration , surgery , chemistry , biochemistry , mathematics , mathematical analysis , gene
Summary Only very few pharmacokinetic (PK) studies comparing plasma derived FVIII (pd‐FVIII) against recombinant FVIII ( rFVIII ) concentrates are available. The studies have been generally conducted to demonstrate the bioequivalence of a new product with an old one. The switch from a plasma‐derived FVIII (pd‐FVIII) to a rFVIII concentrate is a good moment to enrol the patients in a comparative PK study. To achieve information on the PK characteristics of two different classes of FVIII concentrates, according to two different designs: a 10 FVIII concentration/time point design and a reduced 4‐point design. A single dose PK comparing pd‐ and rFVIII concentrates has been performed in four Haemophilia Centres of Italy. Seventeen haemophilia A patients underwent two subsequent single dose PK studies at the moment of switching. Two‐compartment‐ and Non‐compartment‐analysis did not show significant differences between the outcomes of PK of pd‐FVIII and rFVIII , due to inter‐patient variability. In vivo recovery (IVR) of rFVIII was slightly higher than that of pd‐FVIII and rFVIII /pd‐FVIII AUC ratio was 1.37 in 11/17 patients. The difference is only due to the initial distribution phase because after the first 10 h from the end of the infusion, the two decay curves are overlapping. The elimination half‐life of the concentrates was very similar even though a complete bioequivalence was not demonstrated because of a higher AUC of rFVIII concentrates, limited to the distribution phase. The higher C max and IVR of rFVIII may be due to the presence of heterodimers activated forms of the recombinant molecules.