Population Pharmacokinetics of Intravenous Colistin Sulfate in Critically Ill Patients with Pneumonia

To characterize the population pharmacokinetics (PPK) of intravenous colistin sulfate in critically ill patients with pneumonia and explore dosing strategies using model-based simulations.

Ten ICU patients receiving intravenous colistin sulfate for ≥72 h were enrolled. Serial plasma samples were collected after the fifth dose, and unbound concentrations were measured by Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS). Population pharmacokinetic modeling and Monte Carlo simulations were performed.

A total of 130 plasma concentrations were analyzed. Non-compartmental analysis showed a mean C_max,ss of 2.10 ± 0.76 mg/L, AUC_0-12h,ss of 11.57 ± 4.87 h·mg/L, CL_ss of 3.51 ± 2.03 L/h, and t_1/2 of 7.48 ± 3.00 h. A two-compartment model best described the data, with creatinine clearance incorporated as a covariate on clearance. Simulations showed that renal function substantially influenced exposure; at 0.75 MIU every 12 h, simulated fAUC_24h decreased from 49.26 to 20.66 mg·h/L as creatinine clearance increased from 10 to 120 mL/min. Loading doses of 1.0-1.5 MIU increased early plasma concentrations and facilitated rapid target attainment. Clinical success and microbiological eradication were achieved in 80% and 70% of patients, respectively, with no observed nephrotoxicity.

Colistin sulfate pharmacokinetics in critically ill patients were adequately described by a two-compartment model incorporating renal function. These exploratory findings support renal function-guided dosing and suggest a potential role for loading doses, but larger studies are needed to confirm dosing recommendations.