Erythropoietin kinetics in rats: generation and clearance
SE Steinberg, JF Garcia, GR Matzke and J Mladenovic
Detailed studies to analyze the early events of erythropoietin (Ep)
secretion and clearance were performed in a rat model using a double
antibody radioimmunoassay. Ep clearance was determined following
intravenous injection of 1 mL of Ep-rich plasma, 1,080 mU/mL, obtained from
phlebotomized rats. Analysis revealed a disappearance curve that conformed
to a two-compartment model with an alpha half-life t1/2 of 3.6 minutes and
a beta t1/2 of 86 minutes. The volume of distribution was similar to the
calculated plasma volume. In anephric animals, there was no change in the
plasma clearance rate or the volume of distribution. Rapid Ep secretion was
elicited by a single 15 mL/kg phlebotomy (hematocrit decrement 45% to 30%),
so that levels reached 20 to 30 times baseline (524 +/- 76 v 24 +/- 7
mU/mL) at five hours, whereas they plateaued for at least 33 hours. The
increase in the rate of secretion was geometric, from 9.9 mU/h baseline
secretion to 429 mU/h. These data identify a very sensitive and rapidly
responsive system for Ep modulation in the rat.
Volume 67,
Issue 3,
pp. 646-649,
03/01/1986
Copyright © 1986 by The American Society of Hematology
