The present invention relates to methods for determining the in vivo efficiency of a sodium-proton-exchanger (NHE) ion channel ligand comprising the steps of: (a) contacting a cell expressing a sodium-proton-exchanger (NHE) ion channel in vitro with either (i) plasma of an animal and the ion channel ligand or (ii)) the plasma of an animal which has been administered the ion channel ligand; (b) determining the effect of the ion channel ligand on the cell; c) determining ion channel ligand availability by comparing the ligand concentration in the plasma to the concentration of ligand administered; and d) correlating the effect of the ion channel ligand on the cell with the ligand availability to determine the in vivo efficiency of the ligand.