title: Pharmacokinetics and pharmacodynamics of recombinant human granulocyte-colony stimulating factor after intravenous and subcutaneous administration in the rat.
abstract: The pharmacokinetics of recombinant human granulocyte-colony stimulating factor (rhG-CSF) (produced by Kirin Brewery Co., Ltd.) in sera was studied after i.v. and s.c. administration into male Sprague-Dawley rats. Arterial blood samples were taken to determine the rhG-CSF concentrations by measuring its activities using a modified [3H]thymidine assay. After the i.v. dose of 100 micrograms/kg, the half-lives were 25 (alpha) and 102 min (beta). Subcutaneous administration at the 100-micrograms/kg dose resulted in a lower peak serum level but, after 2 hr, rhG-CSF level after the s.c. dose was higher than that of the i.v. dose. The bioavailability of the s.c. dose of 100 micrograms/kg was 78%. The effect of rhG-CSF administration in rats was a specific activity on the neutrophil lineage with increase of neutrophils in peripheral blood. Intravenous and s.c. administration of rhG-CSF had identical effects on the peak neutrophil counts in peripheral blood but, at 24 hr after injection, neutrophil counts after the s.c. dose was greater than that of the i.v. dose. These results indicate the close relationship between pharmacokinetics and pharmacodynamics of rhG-CSF in the rats.
authors: Pharmaceutical Laboratory, Kirin Brewery Co., Ltd., Gunma, Japan.
authors: H
authors: H
authors: Tanaka
authors: Y
authors: Y
authors: Okada
authors: M
authors: M
authors: Kawagishi
authors: T
authors: T
authors: Tokiwa
mesh_terms: D000818:Animals; D003115:Colony-Stimulating Factors / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor; D006410:Hematopoiesis / Q000187:drug effects; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008657:Metabolic Clearance Rate; D051379:Mice; D008809:Mice, Inbred C3H; D009504:Neutrophils / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism
chemical_list: D003115:Colony-Stimulating Factors; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D013936:Thymidine