title: Pharmacodynamics and pharmacokinetics of recombinant human granulocyte colony-stimulating factor (rhG-CSF) after administration of a rectal dosage vehicle.
abstract: The pharmacodynamic activities (leukopoietic effect) and pharmacokinetics of recombinant human granulocyte colony-stimulating factor (rhG-CSF) administered rectally in various doses as hollow-type suppositories were investigated in rabbits. Three kinds of rhG-CSF hollow-type suppositories were employed: suppository I containing rhG-CSF (100-1000 micrograms/kg) in 10 mM acetate buffer solution (ABS) at pH 4.0, suppository II containing rhG-CSF in ABS with alpha-cyclodextrin (alpha-CyD) as an absorption-enhancing agent, and suppository III containing lyophilized rhG-CSF powder. We found that the total count of leukocytes in peripheral blood (total blood leukocyte count) and serum granulocyte colony-stimulating factor (G-CSF) concentration showed a dose-dependent increase. Consequently, the area under the increased total blood leukocyte count-time curve (AUI), an index of pharmacodynamic activity, and the area under the serum G-CSF concentration-time curve (AUC), a pharmacokinetic parameter, increased with an increase in the rhG-CSF dose administered rectally. Good correlation was found between AUL and AUC; thus, it is concluded that an increase in AUC leads to an increase in the effect of rhG-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 suppository) and its leukopoietic effect. The rhG-CSF hollow-type suppository is found to be a promising drug delivery system.
authors.affiliation: Department of Pharmaceutics, Showa College of Pharmaceutical Sciences, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Watanabe
authors.forename: M
authors.initials: M
authors.lastname: Kiriyama
authors.forename: R
authors.initials: R
authors.lastname: Ito
authors.forename: R
authors.initials: R
authors.lastname: Kikuchi
authors.forename: Y
authors.initials: Y
authors.lastname: Mizufune
authors.forename: H
authors.initials: H
authors.lastname: Nomura
authors.forename: M
authors.initials: M
authors.lastname: Miyazaki
authors.forename: M
authors.initials: M
authors.lastname: Matsumoto
mesh_terms: D000285:Administration, Rectal; D000818:Animals; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D006410:Hematopoiesis / Q000187:drug effects*; D006801:Humans; D007962:Leukocytes / Q000187:drug effects* / Q000502:physiology; D008297:Male; D014677:Pharmaceutical Vehicles; D011817:Rabbits; D011994:Recombinant Proteins
chemical_list: D014677:Pharmaceutical Vehicles; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor