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A Human Study to Evaluate Safety, Tolerability, and Cyclic GMP Activating Properties of Cenderitide in Subjects With Stable Chronic Heart Failure
Author(s) -
Kawakami Rika,
Lee Candace Y.W.,
Scott Christopher,
Bailey Kent R.,
Schirger John A.,
Chen Horng H.,
Benike Sherry L.,
Can Valentina,
Martin Fernando L.,
Sangaralingham S. Jeson,
Ichiki Tomoko,
Burnett John C.
Publication year - 2018
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt.974
Subject(s) - cyclic guanosine monophosphate , tolerability , natriuretic peptide , heart failure , pharmacology , medicine , npr1 , guanylate cyclase , receptor , npr2 , adverse effect , blood pressure , guanosine , endocrinology , chemistry , biochemistry , nitric oxide
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.