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First published on April 24, 2009, doi:10.1177/0091270009336233

The Journal of Clinical Pharmacology 2009;49:668.

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©© 2009 American College of Clinical Pharmacology, Inc.
The Journal of Clinical Pharmacology, 10.1177/0091270009336233

Article

Pharmacodynamics of a Novel Designer Natriuretic Peptide, CD-NP, in a First-in-Human Clinical Trial in Healthy Subjects

Candace Y. W. Lee 1, Horng H. Chen 2, Ondrej Lisy 2, Suzanne Swan 3, Courtney Cannon 3, Hsiao D. Lieu 4, and John C. Burnett Jr.2*

1 Cardiorenal Research Laboratory and Mayo Clinic
2 Cardiorenal Research Laboratory
3 DaVita Clinical Research
4 Nile Therapeutics, Inc

* To whom correspondence should be addressed. E-mail: burnett.john{at}mayo.edu.


  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.
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