Absorption, distribution, metabolism and excretion of peginesatide, a novel erythropoiesis-stimulating agent, in rats

摘要: The pharmacokinetics (PK) (absorption, distribution, metabolism, excretion) of peginesatide, a synthetic, PEGylated, investigational, peptide-based erythropoiesis-stimulating agent (ESA), was evaluated in rats. PK profile at 0.1-5 mg·kg(-1) IV using unlabeled or [(14)C]-labeled peginesatide. Mass balance, tissue distribution and metabolism were following administration 5 [(14)C]-peginesatide, with also by quantitative whole-body autoradiography (QWBA) an dose 17 [(14)C]-peginesatide. Plasma clearance slow elimination biphasic unchanged peginesatide representing >90% the total radioactivity radioactive exposure. Slow uptake radiolabeled compound from vascular compartment into tissues observed. Biodistribution to bone marrow extramedullary hematopoietic sites, highly vascularized lymphatic excretory occurred. A predominant degradation event occur vivo loss one PEG chain branched moiety generate mono-PEG. Renal excretion primary mechanism (41%) elimination, parent molecule (67%) major excreted. In conclusion, [(14)C]-peginesatide-derived extended, retention preferentially occurred sites erythropoiesis (bone marrow), urinary route.