PK and PD analyses of eculizumab in patients with PNH. Initiation of eculizumab dosing is indicated at time 0 on the x axis. (A) Serum levels of eculizumab in 11 patients with PNH during the 64 weeks of treatment. The dashed line indicates the level of eculizumab required to completely block complement activity (≥ 35 μg/mL). Time 0 shows levels of eculizumab before (encircled) and 1 hour after dosing, whereas all other time points represent trough values. Two patients with trough levels of eculizumab below 35 μg/mL during the maintenance dosing are identified (patients 1 and 2). (B) Serum hemolytic activity (PD) during the 64-week treatment period, as determined by the ability of serum to lyse antibody-presensitized chicken erythrocytes. The dashed line indicates the percentage of hemolytic activity at which complement is considered effectively inhibited (≤ 20%). Time 0 shows serum hemolytic activity before (encircled) and 1 hour after dosing, whereas all other time points represent trough values. Two patients with trough serum hemolytic activity values above 20% are identified (patients 1 and 2).