Single-and repeat-dose toxicity of HM10760A, a long-acting erythropoietin, in rats and monkeys

Lim, Hyung-Kyu; Choi, Jaehyuk; Kim, Daejin; Bae, Sung Min; Kim, Dae Kyong; Choi, In Young; Kim, Ha Hyung

doi:10.1016/j.taap.2020.115126

Cited by 2 publications

(3 citation statements)

References 28 publications

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“…Upon evaluation of the inoculation site, no signs of damage attributable to the administration of rhEPO were evidenced [25-27]. The only abnormalities detected were clinical signs (hemorrhagic areas) that appeared on the repeated dose toxicity study, but these were related to the method and the reiterative nature of the inoculation rather than to the use of rhEPO itself, since they also appeared with the same intensity in the placebo group [28-30]. The results of the hematological tests were normal when compared to their values before the start of the study.…”

Section: Discussionmentioning

confidence: 99%

Preclinical study of the human recombinant Erythropoietin (GBPD002) compared with Eprex^®

Nag,

Mohiuddin,

Khan

et al. 2024

Preprint

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Erythropoietin (EPO) is a glycoprotein that an essential growth factor for erythroid progenitors at the bone marrow, which appears in blood as a response to hypoxia. It is produced mainly by the kidneys; and its biosynthesis and release are stimulated by the reduction of tissue oxygenation and/or the reduction of the mass of erythrocytes. Here, we report the results of the preclinical evaluation of the safety of ‘GBPD002’ a recombinant human erythropoietin (rhEPO) developed by the Globe Biotech Limited, Bangladesh, through a comparative study of acute toxicity with Eprex®, a commercial homologue from Janssen, UK. The product was administered subcutaneously into Wistar rats, at 500 lU/kg of therapeutic dose (TD) and 3 times of TD for the single dose toxicity study on 14 consecutive days and 125 UL/kg, 250 UL/kg, 500 UL/kg, 750 UL/kg, 1000 UL/kg, 1250 UL/kg and 1500 UL/kg of GBPD002 and Eprex®on 7 consecutive days respectively for the repeated dose toxicity study. Hematological and biochemical parameters were measured for all test subjects before first dose injection and the day after last dose injection of the both studies. Necropsy and histopathology of representative subjects from each group were also observed to find any pathological significance like degeneration or cellular necrosis in internal organs such as kidney, liver, lung and spleen of any rat under experiment. Both GBPD002 and Eprex®comparative toxicology studies revealed similar pharmacologically driven mechanisms of toxicity, which is statistically insignificant (p>0.05). Though hematology parameter values stayed within the normal range during the assay period but the high count of hemoglobin and high hematocrit (P<0.05), together with the decrease in white blood cell, confirm the therapeutic effect of Erythropoietin in both studies. Moreover, in both studies, the initial and final values of aspartate aminotransferase, alanine aminotransferase and blood urea nitrogen were also found similar (p>0.05) for both GBPD002 and Eprex®in the study. The study clearly established that the toxicological profile of “GBPD002” and Eprex®, administered subcutaneously, were similar and related to the known pharmacology of erythropoietin alfa; hereby, demonstrating the proof of ‘totality’ and ‘no residual uncertainty’ between “GBPD002” and Eprex®. Therefore, “GBPD002” and Eprex®shall be administered interchangeably in relevant indications.

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Section: Discussionmentioning

confidence: 99%

Preclinical study of the human recombinant Erythropoietin (GBPD002) compared with Eprex^®

Nag,

Mohiuddin,

Khan

et al. 2024

Preprint

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“…Its main function is to promote red blood cell development and to initiate Hb production (Valent et al, 2018). It is produced in the kidney and stimulates the proliferation and differentiation of committed erythroid progenitors in the bone marrow (Lim et al, 2020) Supplementation Chronic kidney disease (CKD) are characterized by progressive kidney damage and impaired renal function (George et al, 2018) Anemia is a common complication of CKD associated with a decrease in the patient's quality of life. It causes increased morbidity and mortality and accelerates the rate of progression of CKD (George et al, 2018).…”

Section: Methodsmentioning

confidence: 99%

“…In CKD patients, anemia is defined as a situation in which the concentration of hemoglobin (Hb) in the blood is below twice the standard deviation of the average Hb of the general population (Izaks, Westendorp, and Knook, 1999). The hematopoietic cytokine erythropoietin (EPO) regulates the level of circulating red blood cells (RBCs), and treatment with recombinant human EPO (rhEPO) is a breakthrough in the treatment of renal anemia (Lim et al, 2020). EPO is a glycoprotein measuring about 30 kDa with rhEPO is the standard treatment for anemia caused by end-stage renal disease and chemotherapy in cancer patients (Bohlius et al, 2006) Despite the worldwide use of rhEPO, it needs frequent administration because its short half-life has prompted the development of enhanced agent to stimulate erythropoiesis (Mahmood, 2020).…”

Section: Methodsmentioning

confidence: 99%

Non-Pharmacological Interventions for Anemia Treatment: Systematic Review

Putri

Budu

Gemini

et al. 2021

MIPHMP

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The global prevalence of anemia in non-pregnant women, of childbearing age, is estimated at 29.0% and is more common in low- and middle-income countries, women belonging to low socioeconomic strata. iron deficiency can cause direct or risky disability. To determine the effectiveness of Non-Pharmacological Interventions for the treatment of anemia. The method used is with the help of electronic databases from journals that have been published through PubMed, Proquest, EBSCOhost, and Science Direct as many as 6 articles were reviewed from 1186 articles. The 6 articles reviewed in this study with varied respondents using patients, male rats, nurses, Sprague-Dawley (SD) Rattus norvegicus Domestica, bovine serum, premature neonates. Non-pharmacological interventions developed in the treatment of anemia in both human and animal samples as well as the development of treatment and laboratory examinations in the treatment of anemia are Nursing Delirium Screening scale, Hepcidin expression, pain identification, HM10760A, Divalent metal transporter DMT1/SLC11A2, conservative management.

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Single-and repeat-dose toxicity of HM10760A, a long-acting erythropoietin, in rats and monkeys

Cited by 2 publications

References 28 publications

Preclinical study of the human recombinant Erythropoietin (GBPD002) compared with Eprex^®

Preclinical study of the human recombinant Erythropoietin (GBPD002) compared with Eprex^®

Non-Pharmacological Interventions for Anemia Treatment: Systematic Review

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Single-and repeat-dose toxicity of HM10760A, a long-acting erythropoietin, in rats and monkeys

Cited by 2 publications

References 28 publications

Preclinical study of the human recombinant Erythropoietin (GBPD002) compared with Eprex®

Preclinical study of the human recombinant Erythropoietin (GBPD002) compared with Eprex®

Non-Pharmacological Interventions for Anemia Treatment: Systematic Review

Contact Info

Product

Resources

About

Preclinical study of the human recombinant Erythropoietin (GBPD002) compared with Eprex^®

Preclinical study of the human recombinant Erythropoietin (GBPD002) compared with Eprex^®