title: Kinetics of subcutaneous versus intravenous epoetin-beta in dogs, rats and mice.
abstract: The total body clearance of recombinant human erythropoietin (rhEPO) calculated per kilogram of body weight increased in the order man = dog < rat << mouse. The differences disappeared or were reversed when clearance was expressed per square meter of body surface. There was no similar species difference in terminal half life. Total body clearance increased with the dose in dogs and mice, but not in rats. The bioavailability from a subcutaneous depot was 80% in dogs, 76% in rats, and 70% in mice. The absorption from the subcutaneous depot is rapid in rats and mice, but slow in dogs. The pharmacodynamic activity of rhEPO injected by both routes was compared in polycythemic mice. The equipotent doses were 2.44 times higher with intravenous than with subcutaneous injection. Taking into account the bioavailability of 70% from a subcutaneous depot, one obtains a potency ratio of 3.5 for absorbed subcutaneous versus intravenous rhEPO.
authors.affiliation: Department of Drug Research, Boehringer Mannheim GmbH, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Bleuel
authors.forename: R
authors.initials: R
authors.lastname: Hoffmann
authors.forename: B
authors.initials: B
authors.lastname: Kaufmann
authors.forename: P
authors.initials: P
authors.lastname: Neubert
authors.forename: P P
authors.initials: PP
authors.lastname: Ochlich
authors.forename: W
authors.initials: W
authors.lastname: Schaumann
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D003692:Delayed-Action Preparations; D004285:Dogs; D004906:Erythrocyte Count; D004921:Erythropoietin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D011086:Polycythemia / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins; D013045:Species Specificity
chemical_list: D003692:Delayed-Action Preparations; D011994:Recombinant Proteins; D004921:Erythropoietin