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

Objective: To characterize the population pharmacokinetics (PPK) of intravenous colistin sulfate in critically ill patients with pneumonia and explore dosing strategies using model-based simulations. Methods: 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. Results: 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. Conclusion: 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. An infographic showing a three-part workflow read in sequence across three side-by-side sections. Header 1: Critical pneumonia patient population. Text: Colistin Sulfate 0.75 MU q12h. A box reads: CRAB/CRKP/CRPA infection. A second box reads: Renal function differences (CrCL 10-120 mL/min). An illustration shows a hospitalized patient in a bed connected to bedside equipment. Header 2: Two-compartment PPK model (Phoenix NLME). Text: Serial blood sampling → LC-MS/MS. Text: Two-compartment PPK model (Phoenix NLME, CrCL covariate). Icons show blood tubes and the label Plasma, plus an LC-MS/MS instrument with a small plot labeled Intensity and m/z. Header 3: Simulation and validation module. Three boxes read: Dosage recommendation, PK/PD characteristics, Safety.An infographic workflow for colistin sulfate dosing model development and validation in critical pneumonia.