Bioavailability of intravenous versus subcutaneous administration of the dual GC-A and GC-B designer natriuretic peptide cenderitide in healthy canines

Background Heart failure (HF) remains a therapeutic challenge with high morbidity and mortality and frequent hospitalizations. Activators of guanylyl cyclase (GC) A and/or GCB such as naturally occurring or designer natriuretic peptides (NPs) are promising candidates for chronic drug therapy; however, parenteral administration is required. Pumps or subcutaneous administration similar to those used for insulin therapy are an attractive means of enabling chronic peptide delivery. Cenderitide (also known as CD-NP) is a Mayo designed chimeric NP consisting of C-type NP with the C-terminus of Dendroaspis NP currently in clinical development for the treatment of HF. Cenderitide is a dual agonist at both GC-A and GC-B and is relatively resistant to enzymatic degradation. This study was designed to assess the bioavailability of cenderitide when given as a subcutaneous (SQ) bolus as compared to an intravenous (IV) bolus.