A subchronic murine intravenous pharmacokinetic and toxicity study of Hematide™, a PEGylated peptidic erythropoiesis-stimulating agent
| Autor: | Kei-lai Fong, Peter J. Schatz, Susan D. Wilson, Kathryn W. Woodburn, Daniel Norton, Qing Fan |
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| Rok vydání: | 2009 |
| Předmět: |
Male
medicine.medical_specialty No-observed-adverse-effect level medicine.drug_class Health Toxicology and Mutagenesis Polycythemia Pharmacology Toxicology Polyethylene Glycols Mice Pharmacokinetics Bone Marrow Internal medicine medicine Animals No-Observed-Adverse-Effect Level Chemical Health and Safety Hyperplasia Dose-Response Relationship Drug business.industry Public Health Environmental and Occupational Health Half-life General Medicine Erythropoiesis-stimulating agent medicine.disease Extramedullary hematopoiesis Endocrinology medicine.anatomical_structure Hematopoiesis Extramedullary Toxicity Female Bone marrow business Peptides Half-Life |
| Zdroj: | Drug and chemical toxicology. 33(1) |
| ISSN: | 1525-6014 |
| Popis: | The subchronic toxicity of Hematide™, a synthetic PEGylated peptidic erythropoiesis-stimulating agent (ESA), was evaluated in CD-1 mice at intravenous doses of 0, 1, 5, 25, and 125 mg/kg administered once every 3 weeks for 3 months. Hematide displayed sustained plasma levels with reduced clearance and prolonged half-lives up to 59.4 hours that translated into sustained, pronounced polycythemia, bone marrow hyperplasia, and splenic and liver extramedullary hematopoiesis. Toxicological findings were considered to be secondary to exaggerated pharmacology, rather than a direct drug effect, and included mortality at ≥25 mg/kg/dose. The no-observed-adverse-effect-level was determined to be 5 mg/kg. |
| Databáze: | OpenAIRE |
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