A comparative pharmacokinetic and pharmacodynamic study of two novel Cuban PEGylated rHuEPO versus MIRCERA® and ior®EPOCIM
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 (P...
| Autores: | , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2018 |
| País: | México |
| Institución: | Centro de Investigación y de Estudios Avanzados del IPN |
| Repositorio: | Redalyc-CINVESTAV |
| OAI Identifier: | oai:redalyc.org:496055772005 |
| Acceso en línea: | https://www.redalyc.org/articulo.oa?id=496055772005 https://www.redalyc.org/journal/4960/496055772005/ https://www.redalyc.org/journal/4960/496055772005/html/ https://www.redalyc.org/journal/4960/496055772005/496055772005.epub https://www.redalyc.org/journal/4960/496055772005/movil |
| Access Level: | acceso abierto |
| Palabra clave: | Agrociencias non PEGylated EPO reticulocytes Erythropoietin pharmacodynamics |
| Sumario: | 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. |
|---|