President and CEO Clearview Pharma Solutions LLC Plano, Texas
Post-inhalation (PI) cough in Guinea Pig (GP) model was correlated with and predicted by the acidity constant of the chemical stimulant. The test animals were exposed to nebulized solutions of citric and maleic acid. Nonparametric one-way ANOVA (Kruskal-Wallis) of cough counts showed statistically significant dose dependence for both citric acid (p < 0.0001) and maleic acid (p < 0.0001). For citric acid, post-hoc Dunn’s test indicated elevated cough response at the higher concentrations (p≤ 0.0001 for 200 mM, and 300 mM) compared to control (isotonic saline). The GP model can differentiate the cough response of maleic acid vs. citric acid, and the threshold of cough (1-2 coughs in 2 min) for maleic acid (~30 mM) is lower than that for citric acid (~100 mM). The lower threshold of cough for maleic acid as compared to citric acid is consistent with the mechanism of action mediated by protons, in a dose dependent way.
Learning Objectives:
Upon completion, participants will be able to understand the acid-induced post-inhalation cough as relates to physicochemical properties of the chemical entities. This learning can help in subsequent formulation drug development.
Post-inhalation cough can be correlated with and predicted by the acidity constant of the chemical stimulant
The GP model is able to differentiate the cough response of maleic acid vs. citric acid