Comparative pharmacokinetics, safety, and tolerability after subcutaneous administration of recombinant human erythropoietin formulated with different stabilizers
Wk. Cheung et al., Comparative pharmacokinetics, safety, and tolerability after subcutaneous administration of recombinant human erythropoietin formulated with different stabilizers, BIOPHARM DR, 21(6), 2000, pp. 211-219
This report summarizes the results of two double-blind, single-center, rand
omized studies that used a two-period crossover design. The objective of th
ese two studies was to compare the safety, tolerability, pharmacokinetics,
and pain score at the subcutaneous (sc) injection site of a phosphate-buffe
red recombinant human erythropoietin (EPREX (R), epoetin alfa, r-HuEPO) for
mulated with a new stabilizer (glycine and Polysorbate 80) with the commerc
ially available EPREX (R) formulations, which uses human serum albumin (HSA
) as the stabilizer. Twenty-four healthy male volunteers were enrolled in e
ach of the two studies. In the first study, subjects received a single 150
IU/kg sc dose of r-HuEPO using the 2000 IU/mL (2K) phosphate-buffered formu
lation with or without the new stabilizer (12 subjects/group). In the secon
d study, subjects received a single 750 IU/kg sc dose of r-HuEPO using the
40000 IU/mL (40K) phosphate-buffered formulation with or without the new st
abilizer (12 subjects; group). in each study, r-HuEPO was administered over
two separate dosing periods, each separated with a 28-day washout period.
There were no significant differences in AUC and C-max for either strength
of r-HuEPO formulated with or without the new stabilizer, indicating that t
he absorption and disposition characteristics of the two formulations were
similar after sc administration. Both r-HuEPO strengths with and without th
e new stabilizer were safe and well tolerated; the safety and tolerability
profiles of both formulations for each r-HuEPO concentration were comparabl
e. There were no statistically significant differences in pain score for ei
ther strength of r-HuEPO with and without the new stabilizer. It was conclu
ded that the two phosphate-buffered r-HuEPO concentrations formulated with
and without the new stabilizer are pharmacokinetically equivalent. Copyrigh
t (C) 2000 John Wiley & Sons, Ltd.