Comparison of animal models for predicting bronchodilator efficacy in man

In vitro and in vivo models of bronchodilation were compared to assess their relative usefulness for predicting clinical efficacy. Drugs studied were isoproterenol, isoetharine, salbutamol, hexoprenaline, terbutaline, ephedrine and aminophylline. In vitro preparations were guinea pig perfused lung, tracheal strip and spontaneously beating right atria. In vivo, drugs were compared by three routes in conscious guinea pigs and anesthetized dogs and relative potency estimates and separations of bronchodilator and heart rate effects of these agents were determined. The Spearman rank correlation coefficient was statistically significant when the effects of the drugs were compared for guinea pig perfused lung and tracheal responses, in vivo guinea pig and dog intravenous and oral (or intraduodenal) responses. Aerosol results did not correlate, most likely due to differences in experimental techniques. Relative potency estimates were in general agreement with human data in the literature and support the use of these tests for the study of bronchodilator agents.