• Journal of Pharmaceutical Investigation
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• v.31 no.2
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• pp.89-94
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• 2001

The pharmacokinetics of recombinant human granulocyte colony stimulating factor (rhG-CSF) following intravenous (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) administration of HM1041l-lyo and HM10411-liq (lyophilized and liquid formulations of rhG-CSF, recently under development by Hanmi Pharmaceutical Company) were studied in rats, and compared with that of Filgrastim (conventional formulation of rhG-CSF on market). The plasma concentration of rhG-CSF was quantified using a specific ELISA. The pharmacokinetic parameters of rhG-CSF, after i.v., i.m. and s.c. administration of Filgrastim, HM1041l-lyo and HM1041l-liq to rats at a rhG-CSF dose of $10\;{\mu}g/kg$, were almost identical among the three formulations. No dose-dependency was observed in the pharmacokinetic parameters of rhG-CSF following i.v. administration in the dose range of $5{\sim}100\;{\mu}g/kg$. rhG-CSF, after i.v. administration of the three preparations at a dose of $10\;{\mu}g/kg$ to rats, was detected at low levels in all of the body tissues with highest tissue/plasma ratio of $0.46{\sim}0.51$ for the kidney at 30 min after the administration. The pharmacokinetics of rhG-CSF, after i.v. administration to mice at a dose of $10\;{\mu}g/kg$, were comparable among the three formulations. In conclusion, HM10411-lyo and HM10411-liq exhibited similar pharmacokinetics for rhG-CSF with Filgrastim regandless of animal species. Considering the fact that HM10411 series, contrary to Filgrastim, are proteins lacking a methionine residue, the methionine moiety in rhG-CSF molecule does not appear to influence the pharmacokinetics of the protein significantly.

• Journal of Life Science
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• v.21 no.11
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• pp.1652-1657
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• 2011

The production of blood cells is regulated by more than 20 different growth factors, called hematopoitic growth factors. These factors have been produced in prokaryotic and mammalian systems for their clinical use. Glranulocyte-Colony Stimulating Factor (G-CSF) is an important therapeutic factor for cancer patients as well as patients with congenital conditions. These patients do not have enough neutrophils and have a high risk of infection. Two groups of recombinant G-CSF have been used to specially treat cancer patients after chemotherapy because chemotherapy induces neutropenia, a major side effect of chemotherapy drugs. Here, structural and biological characteristics of G-CSF are presented. In addition, the relationship between chemotherapy and neutropenia, which is a severe reduction of neutrophils in the blood, and clinical application of G-CSF is discussed. Recombinant G-CSFs are grouped in two forms. Non-glycosylated G-CSF, filgrastim, is produced in Escherichia coli and glycosylated G-CSF, lenograstim, is produced in Chinese hamster ovary cells. Differences in structure and biological activity are compared and challenges for biosimilar production are also highlighted.

• Korean Journal of Clinical Pharmacy
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• v.25 no.3
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• pp.151-158
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• 2015

Objective: This study was designed to compare pegfilgrastim and filgrastim in diffuse large B-cell lymphoma (DLBCL) patients treated with a rituximab with cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisone (R-CHOP) regimen in terms of clinical efficacy and cost-effectiveness. Method: Clinical efficacy was measured by trough level of absolute neutrophil count (ANC), days of ANC under 50% of baseline value, days of ANC under 90% of baseline value, duration of ANC recovery to baseline value, days of ANC less than $0.5{\times}10^9cells/L$, and difference of peak and trough level of ANC during 1 cycle of R-CHOP regimen. To evaluate cost-effectiveness, total prices of used filgrastim and pegfilgrastim within 1 cycle of R-CHOP were analyzed. Results: In terms of clinical efficacy, trough level of ANC and days to ANC recovery showed statistical significance. The median trough levels of ANC with administration of filgrastim and pegfilgrastim were 0.18 and 1.94 (p = 0.021), respectively, and the median durations of ANC recovery to baseline value were 5.5 days and 2 days (p = 0.023), respectively. For the median days of ANC under 50% of baseline value, days of ANC under 90% of baseline value, days of ANC less than $0.5{\times}10^9cells/L$, and difference of peak and trough level of ANC during 1 cycle of R-CHOP, the pegfilgrastim group performed better than the filgrastim group. However the difference was not statistically significant. In terms of overall expense during 1 cycle of R-CHOP, pegfilgrastim is about 3.43 times more expensive than filgrastim. Conclusion: Pegfilgrastim is more efficient than filgrastim in terms of clinical efficacy. In terms of prices, pegfilgrastim is more expensive than filgrastim for patients, but it is more convenient in clinical use. Therefore, pegfilgrastim should be the preferred choice of G-CSF for neutropenic patients. Further comparative study of pegfilgrastim and filgrastim is needed.

• Toxicological Research
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• v.17 no.2
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• pp.151-157
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• 2001

Neutropenia is a major dose-limiting side effect of cancer chemotherapy. The therapeutic effect of HM 10411 was examined on neutropenia caused by anticancer agents. Neutropenia in normal ICR mice was induced by a single combined intraperitoneal injection of 130 mg/kg of cyclophosphamide (CPA). 4.5 mg/kg of doxorubicin (DXR). and 1 mg/kg of vincristine (VCR) on day O. Neutropenia in tumor-bearing mice was made by a single intraperitoneal injection of 200 mg/kg of cyclophosphamide (CPA) into BALB/c mice bearing Colon 26 adenocarcinoma at 7 day after tumor implantation. HM 10411 or filgrastim (100 $\mu\textrm{g}$/kg/day) was subcutaneously administered for 5 consecutive days starting 1 day after injection of anticancer agents in order to stimulate neutrophil production. Injection of HM 10411 accelerated the recovery from these anticancer drug-induced neutropenia. In normal and tumor-bearing mice. neutrophil production efficacy of HM 10411 was similar than that of filgrastim. These results suggest that HM 10411 could be useful in the clinical treatment for neutropenia induced by anticancer agents.

• The Korean Journal of Nuclear Medicine Technology
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• v.13 no.3
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• pp.17-23
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• 2009

Purpose: It has been known that PET/CT is very valuable in follow-up study of diffuse large B cell lymphoma (DLBCL). Generally, in DLBCL, radiotherapy and chemotherapy has been progressed, because the lesion hasn‘t been limited to one site. And, it has lead to the decrease of leukocyte like neutropenia, due to myelosuppression of chemotherapy. So, in that case, administration of Filgrastim (Granulocyte colony-stimulating factor; G-CSF) is universal. However, in short time after administration, PET/CT has limitation to offer accurate images, through the uptake of $^{18}F$-FDG is increased in the region that is activated bone marrow by hematopoietic growth. Therefore, the aim of this study is that PET/CT in a certain period of time after administration of Filgrastim is able to show normal degree of $^{18}F$-FDG uptake. Materials and Methods: 10 patients under follow-up study of diffuse large B cell lymphoma were examined in this study from January, 2007 to January, 2009 (Male: 4 persons; Female: 6 persons; The mean age: 53.8 years old; The mean weight: 57.3 Kg). Using PET/CT (Discovery STe; GE Healthcare, Milwaukee, WI, USA), whole body images were acquired in 1 hour after $^{18}F$-FDG injection. For image analysis, each ROI ($120\;mm^2$) was drawn on $C^6$ (the sixth C-spine), $L_4$ (the forth L-spine), liver, spleen, and lung, then SUV (Standard Uptake Value)s were measured. We compared with each uptake between in 1-day and 5~7 days after administration of Filgrastim at same patient, so confirmed significance about these by SPSS version 12. Results: In case of $C_6$, $L_4$, spleen, every SUV of 1 day later was remarkably higher than that of 5~7 days later, but liver and lung were similar. Also, the images acquired after 5~7 days distinct remarkably and show normal degree of $^{18}F$-FDG uptake, because uptake of bone was almost disappeared. Conclusions: In this study, each SUV was prominent difference as a period of time after Filgrastim’s administration. And Filgrastim makes concentrate uptake of $^{18}F$-FDG in bone, but, after 5~7 days, bone‘s uptake was greatly decreased. Therefore, we are able to infer a certain period of time that shows normal degree of uptake, by numerical value proven. Also, we consider that this study contribute to advanced study about the other agent like Pegfilgrastim, Lenograstim besides Filgrastim, afterwards.