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

Abstract

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.

• Authors: Candace Y W Lee, Horng H Chen, Ondrej Lisy, Suzanne Swan, Courtney Cannon, Hsiao D Lieu, John C Burnett Jr
• Journal: Journal of clinical pharmacology (J Clin Pharmacol) Vol. 49 Issue 6 Pg. 668-73 (Jun 2009) ISSN: 0091-2700 [Print] England
• PMID: 19395584 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• CD-NP natriuretic peptide
• Cardiovascular Agents
• Elapid Venoms
• Recombinant Fusion Proteins
• Natriuretic Peptide, C-Type
• Sodium
• Cyclic GMP

Topics

• Adult
• Blood Pressure (drug effects)
• Cardiovascular Agents (administration & dosage, adverse effects, pharmacology)
• Cyclic GMP (blood, urine)
• Drug Design
• Elapid Venoms (administration & dosage, adverse effects, pharmacology)
• Female
• Glomerular Filtration Rate (drug effects)
• Humans
• Male
• Middle Aged
• Natriuretic Peptide, C-Type (administration & dosage, adverse effects, pharmacology)
• Recombinant Fusion Proteins (administration & dosage, adverse effects, pharmacology)
• Sodium (urine)