%0 Journal Article
%A Johanna Weiss
%A Walter Emil Haefeli
%T EVALUATION OF INHIBITORY POTENCIES FOR COMPOUNDS INHIBITING P-GLYCOPROTEIN BUT WITHOUT MAXIMUM EFFECTS: F2 VALUES
%D 2006
%R 10.1124/dmd.105.007377
%J Drug Metabolism and Disposition
%P 203-207
%V 34
%N 2
%X In cell culture systems with aqueous buffers, concentration-response curves to lipophilic inhibitors are difficult to establish because plateau effects (Imax) are often not reached because of limited drug solubility. Consequently, the inhibitory potency of a compound will not be definable using IC50 values (concentration exerting 50% of Imax). Since alternative potency measures f2 values, the concentrations required to double baseline signals have been proposed. Using both methods, we reevaluated the concentration-response curves of calcein assays with 78 compounds in three different cell culture systems and found a close correlation between both methods (rs = 0.93–0.99, p ≤ 0.0028). These findings suggest that f2 values are a valuable alternative to define rank orders of highly lipophilic inhibitors as a basis for the prediction of pharmacological interaction properties in clinical settings. Although it was only tested for inhibition of P-glycoprotein, it seems likely that this method may be transferred to other assays with other proteins. The American Society for Pharmacology and Experimental Therapeutics
%U https://dmd.aspetjournals.org/content/dmd/34/2/203.full.pdf