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Pharmacokinetics and tissue distribution of B-domain deleted recombinant human factor VIII (GC-γ AHF) in rats

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Authors
Mar, W.; Kim, K.N.; Choi, E.W.; Fang, M.Z.; Kwak, H.I.; Kim, M.Y.; Son, J.W.; Shin, M.K.; Bae, M.O.; Lee, B.J.; Lee, H.J.; Byun, T.H.; Park, S.Y.; Chun, B.H.; Byun, J.H.; Ahn, G.H.; Lee, Y.J.; Cho, Myung-Haing
Issue Date
2000
Citation
Asia Pacific Journal of Pharmacology, Vol.14 No.1-2, pp.7-10
Keywords
Haemophilia AHuman factor VIIIPharmacokineticsRats
Abstract
Recombinant human factor VIII is a glycoprotein that is used for the treatment of hemophilia A. The B-domain deleted recombinant factor VIII, GC-γ AHF, was newly developed by the Korea Green Cross Pharmaceutical Company. To investigate its pharmacokinetics and tissue distribution, GC-γ AHF was labelled with 125I. Following a single intravenous administration of [125I]GC-γ AHF to rats, plasma concentrations of [125I]GC-γ AHF versus time curves were analyzed and the pharmacokinetic parameters were estimated. The data obtained from plasma as fitted with a two compartment open model and mean residence time (MRT) was 123.83 min. The half life of radioactivity associated with [125I]GC-γ AHF in plasma was 13.25 min and other pharmacokinetic parameters of GC-γ AHF were as follows: Clearance, 23 ml/min/kg; steady-state volume of distribution, 2.84 l/kg. A larger proportion of the administered radioactivity was excreted via urine than via faeces and the total administered dose recovered in excreta was 88.2%. The total levels of radioactivity were higher in liver, stomach and small intestine than in other tissues. These studies suggest that the pharmacokinetic data of GC-γ AHF obtained from rats in the present study would be useful for preclinical evaluation of the newly developed genetically engineered human protein.
ISSN
0217-9687
URI
https://hdl.handle.net/10371/172314
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College of Veterinary Medicine (수의과대학)Dept. of Veterinary Medicine (수의학과)Journal Papers (저널논문_수의학과)
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