Time course of senicapoc plasma concentrations and pharmacodynamic response. (A) Mean changes in hemoglobin level during the 12-week treatment period are plotted versus time for the 3 treatment groups. Mean hemoglobin level changes (± SE) were calculated from baseline hemoglobin values (average of screening and day-1 [before dose] samples). (B) Mean plasma concentrations of senicapoc during the 12-week treatment period are plotted versus time in study patients. Senicapoc levels were expressed as mean values (± SE). Measurements were obtained at day 1 (before dose) and then at the indicated time points during the course of the study for those patients assigned to 1 of the 2 active treatment arms. (C) Effect of senicapoc on the rate of ⁸⁶Rb⁺ flux across the RBC membrane. RBCs were obtained from each of the treatment groups (placebo, 6 mg, 10 mg). Measurements of ⁸⁶Rb⁺ flux due to activation by intracellular calcium were obtained at baseline (average of screening and day 1 [before dose] samples) and then at the indicated time points during the course of the study. Treatment groups are plotted in comparison with whole blood samples spiked with 10 μM senicapoc.