Figure 6.

Dose-Finding Strategy for Equivalence Between Mex and Mex + Booster

(A) Shown are APs at BCL2000, equivalent to Figure 5, at the juncture where the M1652R mutation starts the failure of the repolarization regime. After dose finding, Mex 40 μM gives APD shortening similar to that of Mex 10 μM + booster. (B) APD over the course of 100 cycles at BCL2000. The addition of Mex 10 μM (red trace), induces repolarization at every beat, but EADs persist. This was abolished with Mex 10 μM + booster (blue). To achieve equivalent APD shortening with Mex monotherapy would require Mex 40 μM (gray), a 4-fold increase from the upper therapeutic range of Mex used clinically. APD₉₀ = action potential duration at 90% repolarization; other abbreviations as in Figures 1 and 3.