Diurnal variations in plasma erythropoietin concentration (P-EPO) and urinary erythropoietin excretion (U-EPO), and changes in plasma and urine EPO after administration of recombinant human erythropoietin (rHuEPO) were investigated in normal subjects. Venous blood samples were obtained from 28 healthy subjects (13 males and 15 females) at 9am. P-EPO levels and the hematocrit (Ht) were measured. Blood samples were collected every 4 hours for 24 hours and on day 2, 3, 4, 5 and 7, and urine samples were collected every 4 hours for 24 hours from 5 other males. rHuEPO, 3, 000 units, was then administered intravenously, and rHuEPO, 3, 000 units, was administered subcutaneously to 4 other males. Blood samples and urine samples were collected in the same manner. P-EPO, Ht, the reticulocyte count (Ret) Vand U-EPO were determined. P-EPO was 18.7±1.3mU/m
l (M±SE) in the healthy males and 15.5±1.1mU/m
l in the healthy females, with no significant difference between them. The Ht was 45.2±0.9% in the males and 38.8±0.6% in the females, and the difference was statistically significant. The diurnal levels of P-EPO peaked at 26.1mU/m
l at 4 am. The changes in Ht and Ret were unremarkable. The 24-hour U-EPO level was 17.2±2.4U/day. After intravenous rHuEPO, P-EPO rose to 351.4±32.1mU/m
l 4 hours later and then rapidly decreased to the initial level by 48 hours. The changes in Ht and Ret were unremarkable. U-EPO was 16.4±3.1mU/m
l during the first 4 hours and slowly decreased to the normal value by the next morning. The 24-hour U-EPO level was 52.5±6.4U/day. After subcutaneous rHuEPO, P-EPO increased to 46.4±4.3mU/m
l 8 hours later and returned to initial value by 4 days. The changes in Ht were unremarkable, but Ret was higher on days 5 and 7. Changes in U-EPO were unremarkable. The 24-hour U-EPO level was 16.4±1.9U/day, similar to the value in untreated subjects.
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