Comparative pharmacokinetics, safety, and tolerability after subcutaneous administration of recombinant human erythropoietin formulated with different stabilizers.
This report summarizes the results of two double-blind, single-center, randomized studies that used a two-period crossover design. The objective of these two studies was to compare the safety, tolerability, pharmacokinetics, and pain score at the subcutaneous (sc) injection site of a phosphate-buffered recombinant human erythropoietin (EPREX, epoetin alfa, r-HuEPO) formulated with a new stabilizer (glycine and Polysorbate 80) with the commercially available EPREX formulations, which uses human serum albumin (HSA) as the stabilizer. Twenty-four healthy male volunteers were enrolled in each 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 formulation with or without the new stabilizer (12 subjects/group). In the second study, subjects received a single 750 IU/kg sc dose of r-HuEPO using the 40 000 IU/mL (40K) phosphate-buffered formulation with or without the new stabilizer (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 the absorption and disposition characteristics of the two formulations were similar after sc administration. Both r-HuEPO strengths with and without the new stabilizer were safe and well tolerated; the safety and tolerability profiles of both formulations for each r-HuEPO concentration were comparable. There were no statistically significant differences in pain score for either strength of r-HuEPO with and without the new stabilizer. It was concluded that the two phosphate-buffered r-HuEPO concentrations formulated with and without the new stabilizer are pharmacokinetically equivalent.
Cheung
W K
WK
Department of Drug Metabolism, R.W. Johnson Pharmaceutical Research Institute, 1000 Route 202, South Raritan, NJ, USA.
Natarajan
J
J
Sanders
M
M
Vercammen
E
E
D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004921:Erythropoietin / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D005079:Excipients; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D011863:Radioimmunoassay; D011994:Recombinant Proteins
D005079:Excipients; D011994:Recombinant Proteins; D004921:Erythropoietin