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

W. Mar, K. N. Kim, E. W. Choi, M. Z. Fang, H. I. Kwak, M. Y. Kim, J. W. Son, M. K. Shin, M. O. Bae, B. J. Lee, H. J. Lee, T. H. Byun, S. Y. Park, B. H. Chun, J. H. Byun, G. H. Ahn, Y. J. Lee, M. H. Cho

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)7-10
Number of pages4
JournalAsia Pacific Journal of Pharmacology
Volume14
Issue number1-2
StatePublished - 2000
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmacology

Keywords

  • Haemophilia A
  • Human factor VIII
  • Pharmacokinetics
  • Rats

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