Application of second-order polynomial equations to the study of pharmacodynamic interactions: The effect of flecainide acetate and propranolol on cardiac output and vascular resistance

We have examined the analysis of pharmacodynamic data in normal subjects receiving propranolol, flecainide or the two together. We find that a second-order polynomial describes accurately the response of the left ventricular ejection fraction, cardiac output and vascular resistance of the subjects to these drugs. Both single dose and multiple doses of propranolol (80 mg 3 times a day) decreased the left ventricular ejection fraction and cardiac output, but increased the vascular resistance. On the other hand, single and multiple doses of flecainide (200 mg twice a day) decreased the left ventricular ejection fraction but did not affect either the cardiac output or vascular resistance. These data demonstrate the power of the polynomial formulation in analyzing pharmacodynamic data.