Context: The recombinant human erythropoietin (rHuEPO) stimulates the erythropoiesis process. Because this glycoprotein has a short half-life, it needs to be administrated two to three times a week. One of the technics to solve this issue is the PEGgilation.
Aims: To evaluate the pharmacokinetics (PK) and pharmacodynamics of two new branched PEGylated erythropoietins (i.e., an asymmetric 32 kDa-PEG2-rHuEPO and a symmetric 40 kDa-PEG2-rHuEPO molecule) compared to non-PEGylated ior®EPOCIM and MIRCERA®.
Methods: Serum concentrations of both PEGylated and non-PEGylated erythropoietins were measured at various time points in order to determine PK parameters using non-compartmental analysis approach. The reticulocyte (%), erythrocyte count and hemoglobin levels were ascertained in order to compare the effect of these molecules after administrating a single intravenous dose (10 μg/kg) of each product in male New Zealand rabbits.
Results: Both branched PEGylated erythropoietin forms exhibited half-lives that were significantly longer than ior®EPOCIM (p<0.05), but not statistically different to MIRCERA®. The mean elimination half-life increased from 4 h (ior®EPOCIM) to 131 h for the 32 kDa-PEG2-rHuEPO and 119 h for the 40 kDa-PEG2-rHuEPO. Conversely, MIRCERA® exhibits a half-life of 64 h. Both PEGylated erythropoietin products significantly enhanced the stimulating effect on reticulocytes and erythrocytes formation, as well as on hemoglobin levels, when compared to ior®EPOCIM treatment up to 42 days post-dose.
Conclusions: The PEGylation strategy employed in this study is an effective method to modify the pharmacokinetics and pharmacodynamics of rHuEPO molecule achieving higher half-lives and, therefore, longer in vivo bioactivity. Both of the branched PEGylated-EPO forms tested are promising candidates for human testing.
%0 Journal Article
%1 reynaldo2018comparative
%A Reynaldo, Gledys
%A Rodríguez, Leyanis
%A Menéndez, Roberto
%A Solazábal, Joaquín
%A Amaro, Daniel
%A Becquer, María de los A.
%A Colom, Yamila
%A Gil, Haydee
%A Polo, Juan C.
%A Castañeda, Gilberto
%A Jiménez-Vélez, Braulio
%A Duconge, Jorge
%A Fernández-Sánchez, Eduardo M.
%D 2018
%E JPPRes,
%J Journal of Pharmacy & Pharmacognosy Research
%K PEGylated-EPO erythropoietin non-compartmental-analysis pharmacodynamics pharmacokinetics reticulocytes
%N 3
%P 178-190
%T A comparative pharmacokinetic and pharmacodynamic study of two novel Cuban PEGylated rHuEPO versus MIRCERA® and ior®EPOCIM
%U http://jppres.com/jppres/pdf/vol6/jppres17.342_6.3.179.pdf
%V 6
%X Context: The recombinant human erythropoietin (rHuEPO) stimulates the erythropoiesis process. Because this glycoprotein has a short half-life, it needs to be administrated two to three times a week. One of the technics to solve this issue is the PEGgilation.
Aims: To evaluate the pharmacokinetics (PK) and pharmacodynamics of two new branched PEGylated erythropoietins (i.e., an asymmetric 32 kDa-PEG2-rHuEPO and a symmetric 40 kDa-PEG2-rHuEPO molecule) compared to non-PEGylated ior®EPOCIM and MIRCERA®.
Methods: Serum concentrations of both PEGylated and non-PEGylated erythropoietins were measured at various time points in order to determine PK parameters using non-compartmental analysis approach. The reticulocyte (%), erythrocyte count and hemoglobin levels were ascertained in order to compare the effect of these molecules after administrating a single intravenous dose (10 μg/kg) of each product in male New Zealand rabbits.
Results: Both branched PEGylated erythropoietin forms exhibited half-lives that were significantly longer than ior®EPOCIM (p<0.05), but not statistically different to MIRCERA®. The mean elimination half-life increased from 4 h (ior®EPOCIM) to 131 h for the 32 kDa-PEG2-rHuEPO and 119 h for the 40 kDa-PEG2-rHuEPO. Conversely, MIRCERA® exhibits a half-life of 64 h. Both PEGylated erythropoietin products significantly enhanced the stimulating effect on reticulocytes and erythrocytes formation, as well as on hemoglobin levels, when compared to ior®EPOCIM treatment up to 42 days post-dose.
Conclusions: The PEGylation strategy employed in this study is an effective method to modify the pharmacokinetics and pharmacodynamics of rHuEPO molecule achieving higher half-lives and, therefore, longer in vivo bioactivity. Both of the branched PEGylated-EPO forms tested are promising candidates for human testing.
@article{reynaldo2018comparative,
abstract = {Context: The recombinant human erythropoietin (rHuEPO) stimulates the erythropoiesis process. Because this glycoprotein has a short half-life, it needs to be administrated two to three times a week. One of the technics to solve this issue is the PEGgilation.
Aims: To evaluate the pharmacokinetics (PK) and pharmacodynamics of two new branched PEGylated erythropoietins (i.e., an asymmetric 32 kDa-PEG2-rHuEPO and a symmetric 40 kDa-PEG2-rHuEPO molecule) compared to non-PEGylated ior®EPOCIM and MIRCERA®.
Methods: Serum concentrations of both PEGylated and non-PEGylated erythropoietins were measured at various time points in order to determine PK parameters using non-compartmental analysis approach. The reticulocyte (%), erythrocyte count and hemoglobin levels were ascertained in order to compare the effect of these molecules after administrating a single intravenous dose (10 μg/kg) of each product in male New Zealand rabbits.
Results: Both branched PEGylated erythropoietin forms exhibited half-lives that were significantly longer than ior®EPOCIM (p<0.05), but not statistically different to MIRCERA®. The mean elimination half-life increased from 4 h (ior®EPOCIM) to 131 h for the 32 kDa-PEG2-rHuEPO and 119 h for the 40 kDa-PEG2-rHuEPO. Conversely, MIRCERA® exhibits a half-life of 64 h. Both PEGylated erythropoietin products significantly enhanced the stimulating effect on reticulocytes and erythrocytes formation, as well as on hemoglobin levels, when compared to ior®EPOCIM treatment up to 42 days post-dose.
Conclusions: The PEGylation strategy employed in this study is an effective method to modify the pharmacokinetics and pharmacodynamics of rHuEPO molecule achieving higher half-lives and, therefore, longer in vivo bioactivity. Both of the branched PEGylated-EPO forms tested are promising candidates for human testing.},
added-at = {2018-07-02T10:07:26.000+0200},
author = {Reynaldo, Gledys and Rodríguez, Leyanis and Menéndez, Roberto and Solazábal, Joaquín and Amaro, Daniel and Becquer, María de los A. and Colom, Yamila and Gil, Haydee and Polo, Juan C. and Castañeda, Gilberto and Jiménez-Vélez, Braulio and Duconge, Jorge and Fernández-Sánchez, Eduardo M.},
biburl = {https://www.bibsonomy.org/bibtex/20f58f53fae1c881f19dce95fef21d146/jppres},
editor = {JPPRes},
interhash = {3cc6f672b62a6743c8e77370cc244c67},
intrahash = {0f58f53fae1c881f19dce95fef21d146},
issn = {0719-4250},
journal = {Journal of Pharmacy & Pharmacognosy Research},
keywords = {PEGylated-EPO erythropoietin non-compartmental-analysis pharmacodynamics pharmacokinetics reticulocytes},
language = {English},
month = {May-Jun},
number = 3,
pages = {178-190},
timestamp = {2018-07-02T10:07:26.000+0200},
title = {A comparative pharmacokinetic and pharmacodynamic study of two novel Cuban PEGylated rHuEPO versus MIRCERA® and ior®EPOCIM},
url = {http://jppres.com/jppres/pdf/vol6/jppres17.342_6.3.179.pdf},
volume = 6,
year = 2018
}