Age-Related Differences in Erythropoietic Response to Recombinant Human Erythropoietin: Comparison in Adult and Infant Rhesus Monkeys

Abstract

ABSRACT: Human recombinant erythropoietin (r-HuEPO) was given i.v. to rhesus monkeys to compare its safety, erythropoietic effects, and pharmacokinetics in healthy adult and infant animals. Eighteen adult and 18 infant (9- to 15-d-old) monkeys were divided into three groups each of six animals. One group was given 250 U/kg twice weekly, another was given 100 U/kg twice weekly, and a control group was given the drug vehicle for 6 wk. All animals were healthy throughout this period, and for 10 wk after that. Administration of r-HuEPO at these dosages did not produce any changes in leukocytes, platelets, urea nitrogen, bilirubin, creatinine, alkaline phosphatase, alanine amino transferase, γ-glutamyl transferase, and blood pressure in either age group. At 6 wk, both adult treatment groups had statistically significant increases in Hb concentration. The same dosages that produced these increases in Hb concentration in adults produced no changes in Hb concentration in infant monkeys. Despite active erythropoiesis, as determined by reticulocytosis and increased total body Hb, Hb concentration decreased similarly in the infant treatment and control groups. Pharmacokinetic profiles were obtained at 5 wk of dosing. One h after administration, both doses of r-HuEPO produced significantly lower serum r-HuEPO concentration in the infant monkeys compared with the adults. These differences appeared to be due to a larger volume of distribution of r-HuEPO in the infant monkeys. The t_½ of r-HuEPO in circulation was the same in both age groups.

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