Bioequivalence of two recombinant granulocyte colony-stimulating factor formulations in healthy male volunteers

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 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.

Recombinant Human Granulocyte Colony-Stimulating Factor Promotes Preinvasive and Invasive Estrogen Receptor-Positive Tumor Development in MMTV-erbB2 Mice

“…The transgenic mice were randomly divided into three groups: low-rhG-CSF group (rhG-CSF, 0.125 µg), vehicle-rhG-CSF group (normal saline, 0.25 µg), and high-rhG-CSF group (rhG-CSF, 0.25 µg). These groups are similar to those used in human trials; the peak serum concentrations of G-CSF after administration of a standard dose of G-CSF (5 µg/kg) was found to range from 15 to 30 ng/mL [ 22 23 ]. Four inguinal mammary glands were obtained, spread onto slides, and fixed with 4% formaldehyde overnight after 2 months of treatment.…”

Biologic and molecular effects of granulocyte colony-stimulating factor in healthy individuals: recent findings and current challenges

“…8 In a group of healthy subjects, peak serum levels of G-CSF after the subcutaneous administration of a single 300-g filgrastim dose were 33.4 (Ϯ 7.5) ng/mL. 11 Therefore, while healthy subjects can be exposed during their lifetime to supranormal endogenous G-CSF levels lasting for up to several days with no long-lasting effect, subcutaneous rhG-CSF administration to healthy donors may temporarily boost exogenous G-CSF levels well above the values usually reached under conditions such as bacterial infections. polypeptide and is encoded by a single gene on chromosome 1p35-p34.3.…”

Effects of granulocyte-colony stimulating factor and the expression of its receptor on various malignant cells

“…In the present study, we evaluated the effects of 2 forms of recombinant human G-CSF (rhG-CSF) available for clinical use: filgrastim is derived from Escherichia coli and has a non-glycosylated form, whereas lenograstim is derived from Chinese hamster ovary (CHO) cells and is glycosylated. The peak serum concentrations of G-CSF after administration of a standard dose of G-CSF (5 µg/kg) is found to range from 15 to 30 ng/mL [19, 20]; therefore, we used a range of G-CSF concentrations spanning this concentration (0, 10, 50, and 100 ng/mL). The proliferation effect of G-CSF was prominent in Kasumi-1 cells, and the 2 forms of G-CSF showed similar effects.…”