Effect of Renal Filtration Function on Polymyxin B Pharmacokinetics in Patients with Sepsis

The aim of this study was to investigate pharmacokinetics of polymyxin B (PMB) in patients with sepsis and preserved or impaired renal function.
Methods. A two-center, prospective, randomized study enrolled patients with sepsis. Blood samples for analysis were collected in a steady state (SS) to assess the pharmacokinetics of PMB. PMB concentration in the patients' serum was measured using a direct competitive ELISA to verify the achievement of target area under the concentration-time curve (AUC₂₄) value of 50–100 mg×h/L.
Results. The study included 34 patients with sepsis receiving PMB therapy who were distributed into two groups based on their glomerular filtration rate (GFR): patients with impaired renal function (GFR  80 mL/min, n = 17), and with preserved renal function (GFR  80 mL/min, n = 17). The mean AUC₂₄ value in 34 patients was 64.02 ± 11.64 mg×h/L, the median volume of distribution was 31.53 (23.79–43.72), and the median clearance was 3.72 (2.73–4.85). In patients with preserved renal function, the median AUC₂₄ was 48.38 mg×h/L, and the SS concentration was 2.02 mg/mL. In patients with impaired renal function, the AUC₂₄ was 71.78 mg×h/L, and the SS concentration was 2.99 mg/mL. The clearance of PMB differed considerably depending on GFR: the median clearance in patients with GFR  80 mL/min was 3.28 L/h versus 4.97 L/h in patients with GFR > 80 mL/min (p = 0.012). In 14 of 17 patients with reduced renal function, the AUC₂₄ values fell in the range of 50–100 mg×h/L. In the group with preserved and increased renal function, only 7 of 17 patients reached the target range, and in 53% of patients (9 of 17), the exposure to PMB was below the therapeutic level (AUC₂₄  50 mg×h/L).
Conclusion. Renal function affects the clearance of PMB and, consequently, the achievement of the target therapeutic range. Standard dosing regimens do not provide achieving the target concentrations of antibiotic in all patients, as some patients with preserved renal function have insufficient PMB exposure, while patients with impaired renal function have enhanced exposure, increasing the risk of drug failure or toxicity. To ensure the effectiveness and safety of treatment, regular therapeutic PMB concentrations monitoring and individual dose adjustments are necessary, especially in patients with altered renal function.

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