Influence of human serum albumin content in formulations on the bioequivalency of interferon alfa-2a given by subcutaneous injection in healthy male volunteers.
To determine the influence of human serum albumin (HSA) content in formulations on the bioequivalency of recombinant interferon alfa-2a, a double-blind, randomized, two-way crossover study was conducted in 24 healthy male volunteers. Subjects received a single subcutaneous injection of 18 million IU of Roferon-A reconstituted with either the diluent containing 10 mg of HSA or the HSA-free diluent; final HSA contents in the 2 formulations were 15 mg and 5 mg, respectively. Administration of the 2 formulations resulted in similar 48-hour Roferon-A serum concentration-time profiles and comparable frequency and intensity of adverse events. The statistical analysis using the two one-sided tests procedure showed that both formulations were bioequivalent for pharmacokinetic parameters such as Cmax, tmax, AUC48, and AUC. We conclude that a threefold change in HSA content in formulations does not alter the bioequivalency of Roferon-A.
Zhi
J
J
Hoffmann-La Roche, Inc., Nutley, NJ 07110-1199, USA.
Teller
S B
SB
Satoh
H
H
Koss-Twardy
S G
SG
Luke
D R
DR
D000328:Adult; D004311:Double-Blind Method; D004361:Drug Tolerance; D005079:Excipients; D006801:Humans; D007279:Injections, Subcutaneous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D008297:Male; D011994:Recombinant Proteins; D012709:Serum Albumin / Q000378:metabolism*; D013810:Therapeutic Equivalency
D005079:Excipients; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D012709:Serum Albumin