A Human Study to Evaluate Safety, Tolerability, and Cyclic GMP Activating Properties of Cenderitide in Subjects With Stable Chronic Heart Failure
| Autor: | Tomoko Ichiki, Horng H. Chen, Valentina Cannone, Candace Y.W. Lee, John A. Schirger, Fernando L. Martin, Kent R. Bailey, Christopher G. Scott, John C. Burnett, Sherry L. Benike, S. Jeson Sangaralingham, Rika Kawakami |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Time Factors medicine.drug_class Urinary system Minnesota 030204 cardiovascular system & hematology Pharmacology Kidney Drug Administration Schedule Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Double-Blind Method medicine Natriuretic peptide Cyclic AMP Humans Pharmacology (medical) Prospective Studies Adverse effect Receptor Infusions Intravenous Natriuretic Peptides Cyclic guanosine monophosphate Aged Heart Failure business.industry Research Cardiovascular Agents Articles Middle Aged medicine.disease 3. Good health Renal Elimination 030104 developmental biology Blood pressure Treatment Outcome Tolerability chemistry Heart failure Chronic Disease Female business Biomarkers Glomerular Filtration Rate Snake Venoms |
| Zdroj: | Clinical Pharmacology and Therapeutics |
| ISSN: | 1532-6535 |
| Popis: | Cenderitide is a novel designer natriuretic peptide (NP) composed of C-type natriuretic peptide (CNP) fused to the C-terminus of Dendroaspis natriuretic peptide (DNP). Cenderitide was engineered to coactivate the two NP receptors, particulate guanylyl cyclase (pGC)-A and -B. The rationale for its design was to achieve the renal-enhancing and antifibrotic properties of dual receptor activation, but without clinically significant hypotension. Here we report the first clinical trial on the safety, tolerability, and cyclic guanosine monophosphate (cGMP) activating properties of Cenderitide in subjects with stable heart failure (HF). Four-hour infusion of Cenderitide was safe, well-tolerated, and significantly increased plasma cGMP levels and urinary cGMP excretion without adverse effects with no change in blood pressure. Thus, Cenderitide has a favorable safety profile and expected pharmacological effects in stable human HF. Our results support further investigations of Cenderitide in HF as a potential future cGMP-enhancing therapeutic strategy. |
| Databáze: | OpenAIRE |
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