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Pharmacokinetics of activated recombinant coagulation factor VII (NovoSeven ® ) in children vs. adults with haemophilia A
Author(s) -
Villar A.,
Aronis S.,
Morfini M.,
Santagostino E.,
Auerswald G.,
Thomsen H. F.,
Erhardtsen E.,
Giangrande P. L. F.
Publication year - 2004
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.1365-2516.2004.00925.x
Subject(s) - medicine , pharmacokinetics , haemophilia , haemophilia a , volume of distribution , recombinant factor viia , haemophilia b , coagulation , factor vii , washout , gastroenterology , anesthesia , urology , pharmacology , pediatrics
Summary. To establish the pharmacokinetic profile of activated recombinant coagulation factor VII (rFVIIa; NovoSeven ® ) in children with haemophilia A, and to compare it with the pharmacokinetic profile in adults with haemophilia A. Twelve children (2–12 years) received one single dose of rFVIIa 90 and 180 μ g kg −1 in randomized order separated by a washout period of 48 h to 1 month. Six adults (18–55 years) received a single dose of rFVIIa 90 μ g kg −1 . The pharmacokinetic analyses were based on a non‐compartmental method. In children, the plasma level of FVII increased proportionally with the dose. The total body clearance normalized for body weight was significantly faster in children than in adults (FVII:C, 58 vs. 39 mL kg −1 h −1 and FVIIa, 78 vs. 53 mL kg −1 h −1 , P < 0.05). A trend towards a larger volume of distribution at steady‐state in children than in adults was observed ( P > 0.05). Dose proportionality was established for plasma concentrations of FVII in children with haemophilia A at the dose levels investigated (90 and 180 μ g kg −1 rFVIIa). Following administration of rFVIIa 90 μ g kg −1 , significantly faster clearance was observed in children compared with adults, suggesting that higher doses of rFVIIa may be needed to achieve the same plasma levels as in adults.