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Bioequivalence of two recombinant granulocyte colony‐stimulating factor formulations in healthy male volunteers
Author(s) -
HernándezBernal Francisco,
GarcíaGarcía Idrian,
GonzálezDelgado Carlos A.,
ValenzuelaSilva Carmen,
SotoHernández Ramón,
Ducongé Jorge,
CervantesLlano Majel,
BlancoGarcés Elizabeth,
Rodríguez Víctor,
GarcíaVega Yanelda,
BelloRivero Iraldo,
OliveraRuano Lourdes,
LópezSaura Pedro
Publication year - 2005
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.445
Subject(s) - pharmacokinetics , bioequivalence , pharmacodynamics , crossover study , cmax , medicine , pharmacology , granulocyte colony stimulating factor , confidence interval , white blood cell , chemotherapy , alternative medicine , pathology , placebo
Abstract To evaluate the equivalence of the pharmacokinetic, pharmacodynamic and safety properties of two recombinant G‐CSF formulations in healthy male volunteers, a standard 2‐way randomized crossover double‐blind study, with a 3 week washout period, was conducted. A single 300 µg G‐CSF dose was administered subcutaneously. Hebervital ® (Heber Biotec, Havana, formulation A) and Neupogen ® (Hoffmann‐La Roche S.A, formulation B) were compared. Twenty‐four healthy male volunteers were included. The serum G‐CSF level was measured by enzyme immunoassay (EIA) during the first 36 h after administration. Absolute neutrophils (ANC), white blood cells (WBC) and CD34+ cells counts were the pharmacodynamic variables measured up to 120 h. Other clinical and laboratory determinations were used as safety criteria. The pharmacokinetic parameters for formulation A and B were very close to each other (i.e. AUC , 235.9 vs 270.0 ng·h/ml; C max , 29.2 vs 33.4 ng/ml; T max , 4.2 vs 4.7 h; half‐life, 3.2 vs 2.8 h; CL , 260.9 vs 277.2 ml/h; V d , 1.2 vs 1.1 l; and MRT , 7.58 vs 7.38 h). The confidence intervals for the means ratio of all these parameters were within or very close to the 0.8–1.25 acceptance range. The pharmacodynamics showed high similarity since ANC and WBC had the same profiles for both products and no differences were detected for the estimated parameters. The CD34+ cells count increments were evident for both formulations in a similar way as well. The treatments were well tolerated. Registered adverse events were similar; back/spine pain was the most frequent. According to the overall results these formulations could be considered as clinically comparable. Copyright © 2005 John Wiley & Sons, Ltd.