ERYTHROPOIETIN PHARMACOKINETICS IN PREMATURE-INFANTS - DEVELOPMENTAL,NONLINEARITY, AND TREATMENT EFFECTS

Erythropoietin (EPO) pharmacokinetic studies were performed in prematu re infants (birth weight <1.25 kg) and normal adults. Infants were div ided into two subgroups on the basis of whether they received chronic treatment with recombinant human EPO (rhEPO; 500 IU . kg(-1) . wk(-1) for 6 wk) beginning at 2-4 wk of life. Ten adults and seven rhEPO-trea ted infants underwent intravenous pharmacokinetic studies at escalatin g rhEPO doses: 10, 100, and 500 IU/kg. To test for pharmacokinetic dev elopmental and treatment effects, an equal number of non-EPO- and EPO- treated infants were studied with 100 IU/kg on the last day of treatme nt. Compared with adults, very low birth weight infants demonstrated s ignificantly greater plasma clearance and distribution volume and sign ificantly shorter fractional elimination times (FET) and mean residenc e time (MRT) at all three rhEPO doses. Both infants and adults demonst rated nonlinear EPO elimination, i.e., increasing rhEPO dosing was ass ociated with decreasing plasma clearance and increasing FET and MRT. I n the absence of rhEPO treatment there were no pharmacokinetic differe nces between the two subgroups of infants studied 6 wk apart. In contr ast, the rhEPO-treated infant subgroup demonstrated a significant incr ease in clearance and a decrease in FET and MRT following 6 wk of trea tment. Enhancement of rhEPO efficacy in the prevention and treatment o f anemia in premature infants may require higher doses administered in a progressively increasing fashion.