ArticleEuropean journal of clinical pharmacology2026
Population pharmacokinetics of unbound imipenem in critically ill patients: a comparison of five renal function estimators for PK/PD-guided dosing.
Article in European journal of clinical pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundOptimizing imipenem therapy in intensive care patients presents challenges due to pathophysiological changes affecting drug disposition. This study developed a population pharmacokinetics model, determined optimal dosing strategies, and described the observed pharmacokinetic/pharmacodynamic (PK/PD) target attainment and clinical outcomes.
methodsCritically ill patients receiving imipenem/cilastatin were enrolled prospectively. Five blood samples per patient were collected within 24-48 h of treatment initiation. Nonlinear mixed-effects modeling characterized drug pharmacokinetics, with Monte Carlo simulations assessing target attainment probabilities.
resultsThe study enrolled 21 critically ill patients. A two-compartment model with first-order elimination optimally described imipenem pharmacokinetics, with estimated parameters including total clearance (8.75 L/h), intercompartmental clearance (15.9 L/h), central volume (15.2 L), and peripheral volume (23.4 L). Among evaluated covariates, only estimated glomerular filtration rate (using CKD-EPI 2021 equation) significantly influenced drug clearance. Probability of target attainment analysis (PTA) demonstrated that conventional dosing regimens provided ≥ 90% probability of achieving 40% free time above MIC (fT > MIC) for organisms with MIC values ≤ 2 mg/L. Achieving 75% fT > MIC required maximum conventional doses, whereas 100% fT > MIC with adequate PTA (≥ 80%) necessitated continuous infusion strategies employing doses 30-50% above standard recommendations. Clinical success was observed in 23% of patients (3/13), with higher fT > MIC values among successful cases. However, treatment failure still occurred in some patients despite achieving 100% fT > MIC, suggesting multifactorial determinants of outcomes in critically ill patients.
conclusionRenal function significantly influences imipenem clearance. While standard dosing provides sufficient coverage for conventional PK/PD targets, continuous infusions should be considered for more aggressive targets.
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