[Effects of partial nephrectomy on the pharmacokinetics and pharmacodynamics of recombinant human erythropoietin (SNB-5001) in rats]. 1992

H Masunaga, and R Takahira, and K Kohsaka, and T Sawai
Research Institute of Life Science, Snow Brand Milk Products Co., Tochigi, Japan.

The present study examined the pharmacokinetic and pharmacodynamic profiles of recombinant human erythropoietin (SNB-5001) in partially nephrectomized rats. The plasma level of SNB-5001 was measured by a 2-step enzyme immunoassay. The plasma disappearance curve after intravenous injection of SNB-5001 (50 U/kg) in these rats showed a biexponential pattern similar to that in non-treated rats, conforming to a two-compartment model. However, the total body clearance was reduced, the plasma half life was prolonged and the area under the concentration-time curve of SNB-5001 was increased by the partial nephrectomy. The distribution volumes of SNB-5001 were almost the same as those in non-treated rats. It is suggested that the kidney may contribute to the elimination of SNB-5001. Dose-dependent increases of reticulocytes, red blood cells, hemoglobin and hematocrits were observed after seven repetitive intravenous injections of SNB-5001 in both partially nephrectomized rats and non-treated rats. Hemopoietic responses were calculated by subtracting the initial values from the values after SNB-5001 injections of each hematological parameter (reticulocytes, red blood cells, hemoglobin and hematocrits). Hemopoietic responses in partially nephrectomized rats were apparently stronger than those in non-treated rats. These results suggest that the reduction of clearance by the partial nephrectomy may contribute to the hemopoietic responses, in addition to suggesting that the uremic conditions do not inhibit the effects of SNB-5001 in partially nephrectomized rats.

UI MeSH Term Description Entries
D007668 Kidney Body organ that filters blood for the secretion of URINE and that regulates ion concentrations. Kidneys
D008297 Male Males
D009392 Nephrectomy Excision of kidney. Heminephrectomy,Heminephrectomies,Nephrectomies
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D011994 Recombinant Proteins Proteins prepared by recombinant DNA technology. Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004921 Erythropoietin Glycoprotein hormone, secreted chiefly by the KIDNEY in the adult and the LIVER in the FETUS, that acts on erythroid stem cells of the BONE MARROW to stimulate proliferation and differentiation.
D006207 Half-Life The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. Halflife,Half Life,Half-Lifes,Halflifes
D006410 Hematopoiesis The development and formation of various types of BLOOD CELLS. Hematopoiesis can take place in the BONE MARROW (medullary) or outside the bone marrow (HEMATOPOIESIS, EXTRAMEDULLARY). Hematopoiesis, Medullary,Haematopoiesis,Medullary Hematopoiesis
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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