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