Pharmacokinetics of Cefoperazone/sulbactam in Critically Ill Thrombotic
Thrombocytopenic Purpura Patients Undergoing Therapeutic Plasma Exchange
Abstract
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.