PHARMACODYNAMICS AND PHARMACOKINETICS OF RECOMBINANT HUMAN GRANULOCYTE-COLONY-STIMULATING FACTOR (RHG-CSF) AFTER ADMINISTRATION OF A RECTALDOSAGE VEHICLE

The pharmacodynamic activities (leukopoietic effect) and pharmacokinet ics of recombinant human granulocyte colony-stimulating factor (rhG-CS F) administered rectally in various doses as hollow-type suppositories were investigated in rabbits, Three kinds of rhG-CSF hollow-type supp ositories were employed: suppository I containing rhG-CSF (100-1000 mu g/kg) in 10 mM acetate buffer solution (ABS) at pH 3.0, suppository I I containing rhG-CSF in ABS with alpha-cyclodextrin (alpha-CyD) as an absorption-enhancing agent, and suppository In containing lyophilized rhG-CSF powder, We found that the total count of leukocytes in periphe ral blood (total blood leukocyte count) and serum granulocyte colony-s timulating factor (G-CSF) concentration showed a dose-dependent increa se. Consequently, the area under the increased total blood leukocyte c ount-time curve (AUL), an index of pharmacodynamic activity, and the a rea under the serum G-CSF concentration-time curve (AUC), a pharmacoki netic parameter, increased with an increase in the rhG-CSF dose admini stered rectally. Good correlation was found between AUL and AUC; thus, it is concluded that an increase in AUC leads to an increase in the e ffect of rhc-CSF in inducing leukopoiesis in rabbits following rectal administration. We report for the first time the rectal absorption of rhG-CSF using a new rectal dosage vehicle (rhG-CSF hollow-type supposi tory) and its leukopoietic effect, The rhG-CSF hollow-type suppository is found to be a promising drug delivery system.