Peginesatide clearance, distribution, metabolism, and excretion in monkeys following intravenous administration.

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Woodburn KW, Fong KL, Wilson SD, Sloneker S, Strzemienski P, Solon E, Moriya Y, Tagawa Y

Peginesatide clearance, distribution, metabolism, and excretion in monkeys following intravenous administration.

Drug Metab Dispos. 2013 Apr;41(4):774-84. doi: 10.1124/dmd.112.048033. Epub 2013 Jan 14.

PubMed ID

23318685 [ View in PubMed

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Abstract

Peginesatide, a polyethylene glycol (PEG)ylated peptide-based erythropoiesis-stimulating agent, stimulates the erythropoietin receptor dimer that governs erythropoiesis. Studies were designed to determine the erythropoietic response, pharmacokinetics (PK), tissue distribution, metabolism, and excretion of peginesatide in nonhuman primates following a single i.v. dose. The PK profile of peginesatide (0.1-5 mg/kg) is characterized by low, dose-dependent plasma clearance; small volume of distribution; and long half-life. The peginesatide PK profile following a single i.v. dose is consistent with the sustained erythropoiesis. Biodistribution quantitative whole-body autoradiography demonstrated high peginesatide levels in bone marrow (i.e., primary hematopoietic site) as well as other known hematopoietic sites persisting through at least 3 weeks at 2.1 mg/kg. Microautoradiography analysis at 48 hours postdose revealed uniform and high distribution of radioactivity in the bone marrow and splenic red pulp with less extensive distribution in the renal cortex (glomeruli, associated ducts, interstitial cells). Radioactivity in the kidney was most prominent in the outer medullary and papillary interstitium. At 2 weeks after dosing, cumulative radioactivity recovery in the urine and feces was 60 and 7% of the administered dose, respectively, with most of the radioactivity associated with the parent molecule. In conclusion, the PK characteristics are consistent with a PEGylated peptide of a 45-kDa molecular mass, specifically low volume of distribution and long half-life. Drug was localized principally to hematopoietic sites, and nonspecific tissue retention was not observed. The nonhuman primate data indicate that peginesatide is metabolically stable and primarily excreted in the urine.

DrugBank Data that Cites this Article

Drugs

Peginesatide

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Peginesatide	Erythropoietin receptor	Protein	Humans	Yes	Stimulator	Details