Bioequivalence of two recombinant granulocyte colony-stimulating factor products after subcutaneous injection in healthy volunteers

2009 ◽  
Vol 47 (04) ◽  
pp. 275-282 ◽  
Author(s):  
H. Lubenau ◽  
A. Sveikata ◽  
G. Gumbrevicius ◽  
J. Macijauskiene ◽  
V. Fokas ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Subcutaneous Injection ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Stimulating Factor

scholarly journals Granulocyte colony-stimulating factor administration to healthy volunteers: analysis of the immediate activating effects on circulating neutrophils

Blood ◽  
1994 ◽  
Vol 84 (11) ◽  
pp. 3885-3894 ◽  
Author(s):  
M de Haas ◽  
JM Kerst ◽  
CE van der Schoot ◽  
J Calafat ◽  
CE Hack ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Plasma Levels ◽  
Subcutaneous Administration ◽  
Secretory Vesicles ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Specific Granules ◽  
Stimulating Factor

In four healthy volunteers, we analyzed in detail the immediate in vivo effects on circulating neutrophils of subcutaneous administration of 300 micrograms of granulocyte colony-stimulating factor (G-CSF). Neutrophil activation was assessed by measurement of degranulation. Mobilization of secretory vesicles was shown by a decrease in leukocyte alkaline phosphatase content of the circulating neutrophils. Furthermore, shortly postinjection, Fc gamma RIII was found to be upregulated from an intracellular pool that we identified by immunoelectron microscopy as secretory vesicles. Intravascular release of specific granules was shown by increased plasma levels of lactoferrin and by upregulation of the expression of CD66b and CD11b on circulating neutrophils. Moreover, measurement of fourfold elevated plasma levels of elastase, bound to its physiologic inhibitor alpha 1- antitrypsin, indicated mobilization of azurophil granules. However, no expression of CD63, a marker of azurophil granules, was observed on circulating neutrophils. G-CSF--induced mobilization of secretory vesicles and specific granules could be mimicked in whole blood cultures in vitro, in contrast to release of azurophil granules. Therefore, we postulate that the most activated neutrophils leave the circulation, as observed shortly postinjection, and undergo subsequent stimulation in the endothelial microenvironment, resulting in mobilization of azurophil granules. Our data demonstrate that G-CSF should be regarded as a potent immediate activator of neutrophils in vivo.

scholarly journals Treatment of the anemia of myelodysplastic syndromes using recombinant human granulocyte colony-stimulating factor in combination with erythropoietin [see comments]

Blood ◽  
1993 ◽  
Vol 82 (3) ◽  
pp. 737-743 ◽  
Author(s):  
RS Negrin ◽  
R Stein ◽  
J Vardiman ◽  
K Doherty ◽  
J Cornwell ◽  
...  
Keyword(s):  
Subcutaneous Injection ◽  
Combined Treatment ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Human Erythropoietin ◽  
Cell Counts ◽  
Transfusion Requirements ◽  
Duration Of Disease ◽  
Pretreatment Serum ◽  
Stimulating Factor

Abstract We treated myelodysplastic syndrome patients (MDS) with both recombinant human granulocyte colony-stimulating factor (G-CSF) and recombinant human erythropoietin (EPO) to determine whether such combination therapy resulted in improvement of their anemias. Twenty- four of 28 patients begun on study completed the protocol and were evaluable for erythroid responses. Therapy was initiated with G-CSF at 1 micrograms/kg administered by daily subcutaneous injection and adjusted to either normalize or double the neutrophil count. EPO was then administered by daily subcutaneous injection at a dose of 100 U/kg and dose-escalated to 150 and 300 U/kg every 4 weeks while continuing the G-CSF. Changes in absolute reticulocyte count, hematocrit level, and need for RBC transfusions were compared with pretreatment values as well as other blood cell counts. Ten of 24 patients (42%) had erythroid responses, whereas all patients had neutrophil responses. Six previously transfused patients no longer required RBC transfusions during the treatment period. Erythroid responses were found to be independent of patient age, French-American-British subtype, duration of disease, prior RBC transfusion requirements, or cytogenetic abnormalities at presentation. Pretreatment serum EPO levels were lower in erythroid-responding as compared with nonresponding patients (median 157 v 600 U/L; P = .05). The combined treatment modality was generally well tolerated. We conclude that a substantial percentage of MDS patients had both erythroid and myeloid responses when treated with the combination of G-CSF and EPO.

scholarly journals Treatment of the anemia of myelodysplastic syndromes using recombinant human granulocyte colony-stimulating factor in combination with erythropoietin [see comments]

Blood ◽  
1993 ◽  
Vol 82 (3) ◽  
pp. 737-743 ◽  
Author(s):  
RS Negrin ◽  
R Stein ◽  
J Vardiman ◽  
K Doherty ◽  
J Cornwell ◽  
...  
Keyword(s):  
Subcutaneous Injection ◽  
Combined Treatment ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Human Erythropoietin ◽  
Cell Counts ◽  
Transfusion Requirements ◽  
Duration Of Disease ◽  
Pretreatment Serum ◽  
Stimulating Factor

We treated myelodysplastic syndrome patients (MDS) with both recombinant human granulocyte colony-stimulating factor (G-CSF) and recombinant human erythropoietin (EPO) to determine whether such combination therapy resulted in improvement of their anemias. Twenty- four of 28 patients begun on study completed the protocol and were evaluable for erythroid responses. Therapy was initiated with G-CSF at 1 micrograms/kg administered by daily subcutaneous injection and adjusted to either normalize or double the neutrophil count. EPO was then administered by daily subcutaneous injection at a dose of 100 U/kg and dose-escalated to 150 and 300 U/kg every 4 weeks while continuing the G-CSF. Changes in absolute reticulocyte count, hematocrit level, and need for RBC transfusions were compared with pretreatment values as well as other blood cell counts. Ten of 24 patients (42%) had erythroid responses, whereas all patients had neutrophil responses. Six previously transfused patients no longer required RBC transfusions during the treatment period. Erythroid responses were found to be independent of patient age, French-American-British subtype, duration of disease, prior RBC transfusion requirements, or cytogenetic abnormalities at presentation. Pretreatment serum EPO levels were lower in erythroid-responding as compared with nonresponding patients (median 157 v 600 U/L; P = .05). The combined treatment modality was generally well tolerated. We conclude that a substantial percentage of MDS patients had both erythroid and myeloid responses when treated with the combination of G-CSF and EPO.

scholarly journals Granulocyte colony-stimulating factor (G-CSF) increases histone-complexed DNA plasma levels in healthy volunteers

2016 ◽  
Vol 17 (2) ◽  
pp. 243-249 ◽  
Author(s):  
Christian Schoergenhofer ◽  
Michael Schwameis ◽  
Philipp Wohlfarth ◽  
Christine Brostjan ◽  
Simon T. Abrams ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Plasma Levels ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Stimulating Factor ◽  
Factor G

Continuous subcutaneous injection reduces polymorphonuclear leukocyte activation by granulocyte colony-stimulating factor

2004 ◽  
Vol 286 (1) ◽  
pp. L143-L148 ◽  
Author(s):  
Yukio Sato ◽  
Yukinobu Goto ◽  
Shoko Sato ◽  
Shunsuke Endo ◽  
Yasunori Sohara
Keyword(s):  
Polymorphonuclear Leukocyte ◽  
Subcutaneous Injection ◽  
Bolus Administration ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Single Bolus ◽  
Pmn Elastase ◽  
Csf Levels ◽  
Pmn Élastase ◽  
Stimulating Factor

The use of granulocyte colony stimulating factor (G-CSF) for recovery from neutropenia has been established; however, acute lung injury due to G-CSF-induced polymorphonuclear leukocyte (PMN) activation is a serious complication. This study was designed to compare the activation of PMN with single bolus administration and continuous administration of G-CSF. Healthy volunteers (age 33.8 ± 1.4 yr; n = 6) received a single bolus injection of 50 μm/m2of G-CSF (SI; n = 6) or continuous subcutaneous injection of 50 μm/m2of G-CSF for 24 h (CI; n = 6) and were followed for 48 h. Circulating leukocyte counts, markers of activation on PMN, and circulating levels of G-CSF, IL-6, and PMN elastase were measured. SI rapidly increased serum G-CSF levels, which peaked at 4 h, whereas CI gradually increased G-CSF levels, which remained at a steady level from 8 to 24 h. SI caused a rapid decrease in PMN counts at 0.5 h followed by sustained increase to peak at 12 h. CI gradually increased PMN counts, which peaked at 24 h, but the peak values were not significantly different between the groups. SI-induced activation of PMN, which was characterized by increased expression of CD11b, decreased expression of L-selectin, and increased F-actin content, led to increases in serum IL-6 and PMN elastase level. Such changes were all attenuated with CI ( P < 0.05). We conclude that continuous subcutaneous injection of G-CSF resulted in a marrow response similar to that to a single injection but yielded reduced PMN activation.

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