An HPLC-MS/MS method for determination of sulbactam in human plasma and its pharmacokinetic application in critically ill patients with augmented renal clearance

Augmented renal clearance in critically ill patients can lead to subtherapeutic antibiotic exposure, but data on sulbactam pharmacokinetics in this population are limited. This study developed and validated an HPLC-MS/MS method to measure sulbactam in human plasma, then applied it to characterize sulbactam pharmacokinetics in 11 critically ill patients receiving cefoperazone-sulbactam, comparing those with augmented versus normal renal clearance using Phoenix WinNonlin for non-compartmental analysis. Patients with augmented renal clearance showed a shorter half-life, lower drug exposure (AUC), and higher clearance than those with normal renal function. The findings suggest that higher sulbactam doses should be considered for critically ill patients with augmented renal clearance to maintain adequate drug exposure.