Biomaterial Database

Pharmacokinetic analysis of subcutaneous erythropoietin administration with nonlinear mixed effect model including endogenous production. 1998

N Hayashi, and H Kinoshita, and E Yukawa, and S Higuchi

Clinical Pharmacology Section, Clinical Research & Development Division, Chugai Pharmaceutical Co., Ltd., Tokyo, Japan.

OBJECTIVE Erythropoietin, a glycoprotein hormone is produced by the kidney and targeted to erythrocyte precursors. Recombinant human erythropoietin (Epoetin beta) has been utilized for therapeutic purposes in renal anaemia or anaemia occurring after auto blood donation or chemotherapy. The administration routes for erythropoietin are normally subcutaneous or intravenous. No population pharmacokinetic analysis, however, has been performed following subcutaneous administration with consideration given for endogenous production. METHODS In the present study, we have attempted to analyze the pharmacokinetics of erythropoietin after subcutaneous administration in healthy adult male volunteers by using the Nonlinear Mixed Effect Model program (NONMEM) with a model including endogenous erythropoietin production. RESULTS It has been established that the final estimation of the population mean values of the absorption rate constant (ka), the elimination rate constant (ke), the distribution volume (V) and the endogenous production are 0.0430 h(-1), 0.206 h(-1), 3.141 and 15.7IU h(-1), respectively. For the circadian rhythm of endogenous production, the amplitude was calculated as 9.86% and the peak appeared around 24.00 h. CONCLUSIONS The values for ke and V are very similar to those previously reported for intravenous administration. The circadian rhythm of endogenous production are also able to be substantiated. The factors influencing ke were found to be serum creatinine and age.

UI	MeSH Term	Description	Entries
D007279	Injections, Subcutaneous	Forceful administration under the skin of liquid medication, nutrient, or other fluid through a hollow needle piercing the skin.	Subcutaneous Injections,Injection, Subcutaneous,Subcutaneous Injection
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008297	Male		Males
D008962	Models, Theoretical	Theoretical representations that simulate the behavior or activity of systems, processes, or phenomena. They include the use of mathematical equations, computers, and other electronic equipment.	Experimental Model,Experimental Models,Mathematical Model,Model, Experimental,Models (Theoretical),Models, Experimental,Models, Theoretic,Theoretical Study,Mathematical Models,Model (Theoretical),Model, Mathematical,Model, Theoretical,Models, Mathematical,Studies, Theoretical,Study, Theoretical,Theoretical Model,Theoretical Models,Theoretical Studies
D002940	Circadian Rhythm	The regular recurrence, in cycles of about 24 hours, of biological processes or activities, such as sensitivity to drugs or environmental and physiological stimuli.	Diurnal Rhythm,Nyctohemeral Rhythm,Twenty-Four Hour Rhythm,Nycthemeral Rhythm,Circadian Rhythms,Diurnal Rhythms,Nycthemeral Rhythms,Nyctohemeral Rhythms,Rhythm, Circadian,Rhythm, Diurnal,Rhythm, Nycthemeral,Rhythm, Nyctohemeral,Rhythm, Twenty-Four Hour,Rhythms, Circadian,Rhythms, Diurnal,Rhythms, Nycthemeral,Rhythms, Nyctohemeral,Rhythms, Twenty-Four Hour,Twenty Four Hour Rhythm,Twenty-Four Hour Rhythms
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.
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328	Adult	A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available.	Adults