Nonclinical safety assessment of SPX-101, a novel peptide promoter of epithelial sodium channel internalization for the treatment of cystic fibrosis.

Background: ENaC inhibition has long been an attractive therapeutic target for the treatment of cystic fibrosis. However, previous attempts at developing ENaC inhibitors have been unsuccessful due to complications arising from systemic circulation of the compounds. Here, we describe the preclinical toxicology assessment of a new inhaled peptide promoter of ENaC internalization delivered as a nebulized aerosol.

Cardiorespiratory safety evaluation in non-human primates.

Introduction: This study was designed to provide a comprehensive nonclinical respiratory safety pharmacology assessment using respiratory inductance plethysmography (RIP) concomitant with a standard cardiovascular (CV) safety assessment in non-human primates (NHP) in a single cardiorespiratory study.

Methods: RIP calibration data were generated in conscious, ketamine-sedated, or propofol-anesthetized NHP to determine the most appropriate method. Calibration accuracy was assessed using a CO(2) rebreathe maneuver.

Effects of 4 classes of cardiovascular drugs on ventricular function in dogs with mitral regurgitation.

Background: There have been few trials in which dogs with mitral regurgitation (MR) have been treated with various cardioactive drugs to determine effects on left ventricular (LV) function.

Hypothesis: Four classes of cardiovascular drugs may improve LV function in dogs with MR without increasing MR.

Animals: Nine mature dogs were included in the study.