Journal of Pharmacy & Pharmacognosy Research最新文献

{"title":"A comparative pharmacokinetic and pharmacodynamic study of two novel Cuban PEGylated rHuEPO <i>versus</i> MIRCERA^® and ior^®EPOCIM.","authors":"Gledys Reynaldo,&nbsp;Leyanis Rodríguez,&nbsp;Roberto Menéndez,&nbsp;Joaquín Solazábal,&nbsp;Daniel Amaro,&nbsp;María de Los A Becquer,&nbsp;Yamila Colom,&nbsp;Haydee Gil,&nbsp;Juan C Polo,&nbsp;Gilberto Castañeda,&nbsp;Braulio Jiménez-Vélez,&nbsp;Jorge Duconge,&nbsp;Eduardo M Fernández-Sánchez","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Context: </strong>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.</p><p><strong>Aims: </strong>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^®.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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 <i>in vivo</i> bioactivity. Both of the branched PEGylated-EPO forms tested are promising candidates for human testing.</p>","PeriodicalId":43917,"journal":{"name":"Journal of Pharmacy & Pharmacognosy Research","volume":"6 3","pages":"179-190"},"PeriodicalIF":1.5,"publicationDate":"2018-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6364991/pdf/nihms971091.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36543730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}