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Updated: Jul 23, 2025

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment
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Population pharmacokinetics of polymyxin B in patients with liver dysfunction

Xueyong Li1,2, Yu Cheng1, Bo Chen1,2

  • 1Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, China.

British Journal of Clinical Pharmacology
|July 18, 2023
PubMed
Abstract

Insights

This study developed a population pharmacokinetic model for Polymyxin B (PMB) in liver dysfunction patients. Renal and liver function may not necessitate initial dose adjustments, emphasizing therapeutic drug monitoring for optimal PMB dosing.

Area of Science:

  • Pharmacology
  • Clinical Pharmacy
  • Infectious Diseases

Background:

  • Polymyxin B (PMB) is crucial for treating multidrug-resistant Gram-negative infections.
  • Limited pharmacokinetic data exists for PMB in patients with liver dysfunction.

Purpose of the Study:

  • Develop a population pharmacokinetic (PopPK) model for PMB in patients with liver dysfunction.
  • Identify factors influencing PMB pharmacokinetics in this population.

Main Methods:

  • Retrospective pharmacokinetic study of 136 adult patients with varying liver function.
  • Nonlinear mixed-effects modeling to establish the PopPK model.
  • Monte Carlo simulations for dosage regimen design.

Main Results:

  • A one-compartment model described PMB pharmacokinetics.
  • Creatinine clearance (CrCL) and Child-Pugh class impacted PMB parameters, but dose-normalized exposure variations were not clinically significant.
  • Recommended dosing: 40-75 mg/12-h for MIC ≤0.5 mg/L; doses >100 mg/12-h increase nephrotoxicity risk.

Conclusions:

  • Provides essential PMB pharmacokinetic data for patients with liver dysfunction.
  • Initial dose adjustments for renal and liver dysfunction may not be required.
  • Therapeutic drug monitoring (TDM) is more critical than PopPK-guided adjustments for optimizing PMB dosing within its therapeutic window.
Keywords:
Monte Carlo simulationliver dysfunctionpolymyxin Bpopulation pharmacokinetics

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