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Pharmacokinetics and pharmacodynamics of turoctocog alfa and N8 ‐ GP in haemophilia A dogs
Author(s) -
Agersø H.,
Stennicke H. R.,
Pelzer H.,
Olsen E. N.,
Merricks E. P.,
deFriess N. A.,
Nichols T. C.,
Ezban M.
Publication year - 2012
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/j.1365-2516.2012.02896.x
Subject(s) - pharmacodynamics , medicine , pharmacokinetics , dosing , pharmacology , haemophilia , partial thromboplastin time , platelet , surgery
Summary The objective of the present study was to evaluate the pharmacokinetic ( PK ) and pharmacodynamic ( PD ) profiles of the new recombinant FVIII compound turoctocog alfa and a Glyco‐PEGylated FVIII derivative thereof ( N8‐GP ) in Haemophilia A dogs. Six haemophilic dogs divided into two groups were included in the study. Each dog was administered a dose of 125 U kg −1 , blood samples were collected at predetermined time points for both pharmacokinetic ( FVIII measured by one‐stage aPTT assay) and pharmacodynamic [whole blood clotting time ( WBCT )] evaluations. After intravenous administration to haemophilic dogs, the plasma concentration at the first sampling point was comparable for turoctocog alfa and N8‐GP , and the clearance was estimated to be 6.5 and 3.9 mL h −1 kg −1 for turoctocog alfa and N8‐GP respectively. Both turoctocog alfa and N8‐GP were able to reduce the WBCT time to normal levels (<20 min), however, the reduced clearance was reflected in the WBCT , which returned to baseline at a later time point for N8‐GP as compared with dogs dosed with turoctocog alfa. The clearance was 40% reduced for N8‐GP as compared with turoctocog alfa. Simulations of a multiple dosing regimen in dogs, suggest that to maintain WBCT <20 min N8‐GP can be dosed at reduced intervals, e.g. with 4 days between doses, whereas turoctocog alfa will have to be dosed with 2½ day between doses. Data thereby supports N8‐GP as an alternative to standard rFVIII replacement therapy, with a more convenient dosing regimen.