Erythropoietin pharmacokinetics in premature infants:
developmental, nonlinearity and treatment effects.
Widness, John A., Peter Veng-Pedersen, Charles Peters, Luis M.
Pereira,.
Robert L. Schmidt, and Lance S. Lowe
APStracts 2:0401A, 1995.
Erythropoietin (EPO) pharmacokinetic studies were performed in
premature infants (birth weight <1.25 kg) and normal adults.
Infants were divided into two subgroups based on whether or not they
received chronic treatment with r-HuEPO (500 IU r-HuEPO/kg-wk for six
weeks) beginning at 2-4 weeks of life. Ten adults and seven r-HuEPO
treated infants underwent intravenous pharmacokinetic studies at
escalating r-HuEPO doses: 10, 100, and 500 IU/kg. To test for
pharmacokinetic developmental and treatment effects, an equal number
of non-EPO- and EPO-treated infants were studied with 100 IU/kg on
the last day of treatment. Compared to adults, VLBW infants
demonstrated significantly greater plasma clearance and distribution
volume, and significantly shorter fractional elimination times (FET)
and mean residence time (MRT) at all three r-HuEPO doses. Both
infants and adults demonstrated nonlinear EPO elimination, i.e.,
increasing r-HuEPO dosing was associated with decreasing plasma
clearance and increasing FET and MRT. In the absence of r-HuEPO
treatment there were no pharmacokinetic differences between the two
subgroups of infants studied six weeks apart. In contrast, the r
-HuEPO treated infant subgroup demonstrated a significant increase in
clearance and a decrease in FET and MRT following six weeks of
treatment. Enhancement of r-HuEPO's efficacy in the prevention and
treatment of anemia in premature infants may require higher doses
administered in a progressively increasing fashion.
Received 5 July 1995; accepted in final form 1 September 1995.
APS Manuscript Number A716-5.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 September 1995.