Bioequivalence of two recombinant granulocyte colony-stimulating factor formulations in healthy male volunteers.
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 microg 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.
Hernández-Bernal
Francisco
F
Clinical Trials Division, Center for Biological Research, Atabey, Playa, Havana, Cuba.
García-García
Idrian
I
González-Delgado
Carlos A
CA
Valenzuela-Silva
Carmen
C
Soto-Hernández
Ramón
R
Ducongé
Jorge
J
Cervantes-Llano
Majel
M
Blanco-Garcés
Elizabeth
E
Rodríguez
Víctor
V
García-Vega
Yanelda
Y
Bello-Rivero
Iraldo
I
Olivera-Ruano
Lourdes
L
López-Saura
Pedro
P
D000328:Adult; D018952:Antigens, CD34 / Q000378:metabolism; D019540:Area Under Curve; D001416:Back Pain / Q000139:chemically induced; D018592:Cross-Over Studies; D004311:Double-Blind Method; D016179:Granulocyte Colony-Stimulating Factor / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D007279:Injections, Subcutaneous; D007958:Leukocyte Count; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects; D008297:Male; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D011994:Recombinant Proteins; D013810:Therapeutic Equivalency
D018952:Antigens, CD34; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor