Pharmacokinetics and distribution of recombinant erythropoietin in rats.
Pharmacokinetics and distribution of recombinant human erythropoietin (rh-EPO, Epoch, CAS 11096-26-7) were studied in rats. After intravenous administration, concentrations of rh-EPO in the plasma declined biexponentially. AUC increased proportionally with the dose. The half-life of a-phase was prolonged with increasing doses. The low volume (Vss) of the distribution of rh-EPO was 65-79 ml/kg, which indicate a mainly extracellular distribution of this drug. The half-life of beta-phase was 1.98-2.7 h. The total body clearance was 18-21 ml/h/kg, and was independent of the dose. The renal clearance was much lower than total body clearance, suggesting that extrarenal clearance, presumably metabolism, plays a role in elimination. rh-EPO was eliminated by metabolism. The profiles of times vs concentration of radioactivity in the bone marrow and spleen, which are considered to be target tissues, were different from that of the plasma; namely bone marrow and spleen showed Cmax at 30 min after dosing, and this time, radioactivity in these tissues showed almost intact rh-EPO. At the dose of 0.1 micrograms/kg, the concentration in the bone marrow was about 2-fold higher than that of plasma, the concentration in the spleen was lower than that in the plasma 30 min after dosing of rh-EPO. The distributions of rh-EPO in both tissues were saturable.
Kinoshita
H
H
Drug Metabolism Laboratory, Chugai Pharmaceutical Co., Ltd., Tokyo, Japan.
Ohishi
N
N
Kato
M
M
Tokura
S
S
Okazaki
A
A
D000818:Animals; D016466:CHO Cells; D002850:Chromatography, Gel; D006224:Cricetinae; D004921:Erythropoietin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006207:Half-Life; D007275:Injections, Intravenous; D007457:Iodine Radioisotopes; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics; D014018:Tissue Distribution
D007457:Iodine Radioisotopes; D011994:Recombinant Proteins; D004921:Erythropoietin