Population pharmacokinetics of intravenous colistin sulfate and dosage optimization in critically ill patients

Colistin sulfate dosing in critically ill patients requires careful optimization given its narrow therapeutic window, but population pharmacokinetic data to guide this were limited. This study analyzed 98 plasma concentrations from 20 critically ill patients receiving intravenous colistin sulfate to build a population pharmacokinetic model using Phoenix NLME, then used Monte Carlo simulation to evaluate dosing regimens. Creatinine clearance and alanine aminotransferase were significant covariates, and simulations revealed that the labeled dosing regimen (1.0-1.5 million units daily) was insufficient for patients with normal renal function or higher-MIC pathogens. The findings suggest colistin sulfate dosing should be adjusted based on renal function and drug exposure rather than following a fixed labeled regimen.