AIMS The aim of this study was to investigate the pharmacokinetics of CFP and SUL in critically ill thrombotic thrombocytopenic purpura (TTP) patients undergoing TPE. METHODS Critically ill TTP patients receiving a dose of 3 g CFP/SUL (2.0 g/1.0 g) intravenously every 8 h were included in the study. Serial blood samples were collected at 0, 1, 2, 3, 4, 6, and 8 h at the third infusion with TPE (Session I) and the sixth infusion without TPE (Session II). Effluent samples were also collected at the effluent port of plasma eliminated during TPE. Concentrations of CFP and SUL in plasma and effluent were measured using LC/MS/MS. RESULTS Specific pharmacokinetic parameters were calculated to evaluate the effect of TPE on CFP and SUL. The amount of drug eliminated during TPE (QPE) were 395.75±147.38 and 35.25±11.32 mg, respectively. Percentage eliminated by TPE (fe%) were 11.38±3.18% and 2.74±1.13%, respectively. Calculated percentages of total drug clearance by TPE (%CLPE) were 27.71±10.8% and 6.16±2.16%, respectively. There were no significant differences in pharmacokinetic parameters (AUC0-8, Vd, T1/2a) between session I and session II for both CFP and SUL. CONCLUSIONS A single plasma volume TPE does not remove clinically significant amounts of CFP and SUL. Dosage adjustment in critically ill TTP patients after the procedure is not necessary. CFP is more likely to be removed than SUL during TPE due to its small Vd and high protein binding (Pb). Elevated plasma drug concentration due to organ dysfunction may permit more drug removal during TPE.