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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.JD

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.

Authors+Show Affiliations

Department of Pharmaceutics, Showa College of Pharmaceutical Sciences, Tokyo, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

8705257

Citation

Watanabe, Y, et al. "Pharmacokinetics and Pharmacodynamics of Recombinant Human Granulocyte Colony-stimulating Factor (rhG-CSF) Following Intranasal Administration in Rabbits." Journal of Drug Targeting, vol. 3, no. 3, 1995, pp. 231-8.
Watanabe Y, Matsumoto Y, Kikuchi R, et al. 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.
Watanabe, Y., Matsumoto, Y., Kikuchi, R., Kiriyama, M., Nakagawa, K., Nomura, H., Maruyama, K., & Matsumoto, M. (1995). Pharmacokinetics and pharmacodynamics of recombinant human granulocyte colony-stimulating factor (rhG-CSF) following intranasal administration in rabbits. Journal of Drug Targeting, 3(3), 231-8.
Watanabe Y, et al. 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. PubMed PMID: 8705257.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacokinetics and pharmacodynamics of recombinant human granulocyte colony-stimulating factor (rhG-CSF) following intranasal administration in rabbits. AU - Watanabe,Y, AU - Matsumoto,Y, AU - Kikuchi,R, AU - Kiriyama,M, AU - Nakagawa,K, AU - Nomura,H, AU - Maruyama,K, AU - Matsumoto,M, PY - 1995/1/1/pubmed PY - 1995/1/1/medline PY - 1995/1/1/entrez SP - 231 EP - 8 JF - Journal of drug targeting JO - J Drug Target VL - 3 IS - 3 N2 - 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. SN - 1061-186X UR - https://www.unboundmedicine.com/medline/citation/8705257/Pharmacokinetics_and_pharmacodynamics_of_recombinant_human_granulocyte_colony_stimulating_factor__rhG_CSF__following_intranasal_administration_in_rabbits_ L2 - https://www.tandfonline.com/doi/full/10.3109/10611869509015950 DB - PRIME DP - Unbound Medicine ER -