Studies on the metabolic fate of recombinant human erythropoietin(SNB-5001). I: Changes of plasma level measured by enzyme-immunoassay in rats and dogs after single intravenous and subcutaneous injection of SNB-5001.

Abstract

Time courses of plasma levels were examined using two-steps enzyme-immunoassay(EIA) in rats and dogs after single intravenous or subcutaneous injection of recombinant human erythropoietin (SNB-5001). After intravenous injection of SNB-5001 to rats and dogs, the plasma level declined biexponentially, well described by a two-compartment model. Plasma half lives of rapid phase and slower phase were 0.7 ?? 1hr(t1/2α) and 1.8 ?? 6hr(t1/2β) in rats, and 1 ?? /1.7hr (t1/2α) and 4.3 ?? 10.1hr (t1/2β) in dogs, respectively, after single intravenous injection in dosing range from 50 to 1250U/kg of SNB-5001. Plasma level profiles in female dogs were similar to those in male dogs after intravenous injection of SNB-5001. After the subcutanous injection of SNB-5001, plasma levels gradually increased showing a dose-dependent Cmax values. Tmax was 6 ?? 7hr in rats and 7 ?? 13hr in dogs. Plasma levels of SNB5001 determined by EIA showed a good correlation with the levels of biological activity determined by in vitro bioassay. Plasma SNB-5001 levels after subcutaneous injection declined slower than those after intravenous injection in rats and dogs. Plasma half lives in dogs were longer than those in rats after both intravenous and subcutaneous injection of SNB5001. The area under the plasma concentration-time curve increased in dose-dependent manner after intravenous and subcutaneous injection of SNB-5001 in rats and dogs. Bioavailabilities after subcutaneous injection were 50 ?? 60% in rats and 40 ?? 70% in dogs.