Pharmacodynamics of a novel designer natriuretic peptide, CD-NP, in a first-in-human clinical trial in healthy subjects

• Published in: Journal of clinical pharmacology Vol. 49; no. 6; p. 668
• Main Authors: Lee, Candace Y W, Chen, Horng H, Lisy, Ondrej, Swan, Suzanne, Cannon, Courtney, Lieu, Hsiao D, Burnett, Jr, John C
• Format: Journal Article
• Language: English
• Published: England 01.06.2009
• Subjects: Adult; Blood Pressure - drug effects; Cardiovascular Agents - administration & dosage; Cardiovascular Agents - adverse effects; Cardiovascular Agents - pharmacology; Cyclic GMP - blood; Cyclic GMP - urine; Drug Design; Elapid Venoms - administration & dosage; Elapid Venoms - adverse effects; Elapid Venoms - pharmacology; Female; Glomerular Filtration Rate - drug effects; Humans; Male; Middle Aged; Natriuretic Peptide, C-Type - administration & dosage; Natriuretic Peptide, C-Type - adverse effects; Natriuretic Peptide, C-Type - pharmacology; Recombinant Fusion Proteins - administration & dosage; Recombinant Fusion Proteins - adverse effects; Recombinant Fusion Proteins - pharmacology; Sodium - urine
• ISSN: 0091-2700
• DOI: 10.1177/0091270009336233

CD-NP is a novel chimeric natriuretic peptide (NP) consisting of the 22-amino-acid (AA) human C-type natriuretic peptide (CNP), a venodilating peptide with limited renal actions and minimal effects on blood pressure, and the 15-AA C-terminus of Dendroaspis NP (DNP). The rationale for the design of CD-NP was to enhance the renal actions of CNP, the ligand for natriuretic peptide receptor-B, but without inducing excessive hypotension. Here we report the first-in-human studies for CD-NP, which represent the first successful clinical testing of a chimeric NP demonstrating in normal human volunteers that CD-NP possesses cyclic guanosine monophosphate-activating, natriuretic, and aldosterone-suppressing properties without inducing excessive hypotension, laying the foundation for additional studies on this first-in-class new cardiovascular therapeutic in human heart failure, which are now underway worldwide.