ABSORPTION ENHANCEMENT OF POLYPEPTIDE DRUGS BY CYCLODEXTRINS .4. ABSORPTION AND BLOOD LEUKOCYTE DYNAMICS OF RECOMBINANT HUMAN GRANULOCYTE-COLONY-STIMULATING FACTOR (RHG-CSF) FROM INTRANASALLY ADMINISTERED PREPARATIONS CONTAINING RHG-CSF AND CYCLODEXTRINS IN RABBITS

The absorption of recombinant human granulocyte colony-stimulating fac tor (rhG-CSF) and blood leukocyte dynamics following intranasal (i.n.) administration of aqueous preparations containing rhG-CSF with or wit hout cyclodextrins (CyDs) were investigated in conscious rabbits by me asuring the serum G-CSF concentration and the total number of leukocyt es in peripheral blood. Serum G-CSF concentration was rapidly increase d by coadministration of rhG-CSF and CyD, particularly, alpha and beta types. The total number of leukocytes in peripheral blood also increa sed (the maximum level of approx. 20000/mu l was attained 24 h after a dministration) and exceeded physiological levels (5200-12000/mu l) in rabbits. The increase in the number of leukocytes was observed between approx. 8 and 48 h after i.n. administration. These results suggest t hat rhG-CSF is efficiently absorbed through the nasal mucosa. It may b e concluded that the development of a rhG-CSF delivery system could be achieved in the form of the nasal administration of rhG-CSF with CyDs .