Pharmacokinetics and distribution of recombinant human erythropoietin in rats with renal dysfunction.
Pharmacokinetics and distribution were studied following intravenous administration of recombinant human erythropoietin (rh-EPO, CAS 11096-26-7) to 5/6-nephrectomized rats. 5/6-Nephrectomy caused a significant decrease of total body clearance of rh-EPO. Renal function, therefore, is thought to affect the metabolism in extrarenal tissues. The metabolism of EPO might be indirectly associated with renal function. There were no differences of the concentration in the bone marrow and spleen between 5/6-nephrectomized rats and non-nephrectomized rats, suggesting that 5/6-nephrectomy does not cause a change in the affinity of rh-EPO for target tissues. Repeated administration of rh-EPO caused a slight reduction of the biological half-life in 5/6-nephrectomized rats as well as in non-nephrectomized rats, suggesting stimulation of a compensatory metabolism in extrarenal tissues.
Kinoshita
H
H
Drug Metabolism Laboratory, Chughai Pharmaceutical Co., Ltd., Tokyo, Japan.
Ohishi
N
N
Tokura
S
S
Okazaki
A
A
D000818:Animals; D004921:Erythropoietin / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D007457:Iodine Radioisotopes; D007674:Kidney Diseases / Q000378:metabolism*; D008297:Male; D009392:Nephrectomy; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000493:pharmacokinetics
D007457:Iodine Radioisotopes; D011994:Recombinant Proteins; D004921:Erythropoietin