Pharmacokinetics and pharmacodynamics of recombinant human granulocyte colony-stimulating factor (rhG-CSF) following intranasal administration in rabbits

J Drug Target. 1995;3(3):231-8. doi: 10.3109/10611869509015950.

Abstract

The objective of this study was to evaluate the pharmacokinetics and pharmacodynamics of G-CSF as well as their relationship following intranasal (i.n.) administration of aqueous rhG-CSF preparations with or without additives. In order to achieve a better understanding of the dosage regimen and the effectiveness of intranasally administered rhG-CSF in inducing leukopoiesis, we investigated rhG-CSF absorption and blood leukocyte dynamics with respect to dose in rabbits. RhG-CSF could be absorbed through the nasal cavity of rabbits when rhG-CSF aqueous preparations, especially those containing alpha-cyclodextrin (alpha-CyD) were intranasally administered. We found that serum G-CSF levels and the total count of leukocytes in peripheral blood (total blood leukocyte count) showed a dose-dependent increase with rhG-CSF. The area under the serum G-CSF concentration-time curve (AUC, a pharmacokinetic parameter) and the area under the increased total blood leukocyte count-time curve (AUL, a pharmacodynamic parameter) increased with increase of dose of rhG-CSF administered intranasally. Good agreement was observed between log AUC and AUL; thus, it is concluded that an increase of AUC leads to an increase in effectiveness of rhG-CSF in inducing leukopoiesis in rabbits. A novel rhG-CSF delivery system in the form of i.n. administration of rhG-CSF was thus achieved.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Intranasal
  • Animals
  • Cyclodextrins / pharmacology
  • Granulocyte-Macrophage Colony-Stimulating Factor / blood
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacokinetics*
  • Half-Life
  • Leukocyte Count / drug effects
  • Male
  • Metabolic Clearance Rate / drug effects
  • Rabbits
  • Recombinant Proteins / pharmacokinetics
  • alpha-Cyclodextrins*

Substances

  • Cyclodextrins
  • Recombinant Proteins
  • alpha-Cyclodextrins
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • alpha-cyclodextrin