Abstract
Nasal and pulmonal absorption of recombinant human granulocyte colony-stimulating factor (rhG-CSF) was examined in the rat. After the intranasal and intratracheal administration, the relative bioavailability of rhG-CSF for subcutaneous administration was about 2% and about 27%, respectively, as evaluated area under the curve (AUC) of the plasma rhG-CSF concentration versus time for 8 hr. The pharmacological availability relative to subcutaneous administration was determined from the increase in the total blood leukocyte numbers. The pharmacological availability was 5-10% after the intranasal administration, determined from the AUC for the increased ratio of the total leukocyte numbers versus time for 48hr; it was slightly dependent on the pH and osmotic pressure of dosing solution. After the pulmonal absorption, on the other hand, the pharmacological availability was equal to or more than the availabilities after intravenous and subcutaneous administration; under pH6.5 and isotonic osmolarity, the availability was minimal. In comparison with the above two prenternal administration routes for rhG-CSF, the intratracheal administration was more efficient than the intranasal administartion. Laureth-9 increased the bio-availability and pharmacological availability in both nasal and pulmonary absorption of rhG-CSF, but sodium glycocholate was effective only in the pulmonary absorption. Some protease inhibitors were effective in the pulmonary absorption but not in the nasal absorption.
