ArticleClinical pharmacokinetics2025
A Population Pharmacokinetic Analysis for Piperacillin/Tazobactam in Patients with End-Stage Kidney Disease Undergoing Intermittent Haemodialysis: Extension of a General-Purpose Model.
Article in Clinical pharmacokinetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Who cites it
1 citing paper in PubMed.
- Evaluation of a model averaging algorithm for model-informed precision dosing in the context of parameter misspecifications.Journal of pharmacokinetics and pharmacodynamics · 2026Article
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7 authors.
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Abstract
BACKGROUND AND
objectiveEnd-stage kidney disease (ESKD) patients undergoing haemodialysis (HD) require a dosing regimen that balances the low endogenous clearance with the additional dialyser clearance. This study aimed to expand a previously proposed general-purpose pharmacokinetic model for piperacillin/tazobactam with a new population of ESKD patients undergoing intermittent high-flux haemodialysis.
methodsInter- and intradialytic blood samples were collected in ESKD patients undergoing intermittent high-flux haemodialysis, in HD or haemodiafiltration (HDF) mode, who received piperacillin/tazobactam during routine care. The previous general-purpose model was expanded to reflect changes in the pharmacokinetics in the new patient population. A covariate search was performed focussing on factors that explained variability between patients in endogenous and dialysis clearance. Simulations were performed to determine the probability of target attainment with current dosing recommendations in this specific population.
resultsIn 20 ESKD patients, 195 piperacillin/tazobactam concentrations were determined. The general-purpose model was successfully expanded, wherein endogenous piperacillin/tazobactam clearance in patients with/without residual diuresis was 63% (95% confidence interval [CI] 49.5-73.0%) and 78.6% (95% CI 66.3-86.4%) lower compared with the general population, respectively. Extraction ratios of piperacillin and tazobactam ranged from 64 to 80%. Differences in probability of target attainment (PTA) for piperacillin were observed between patients with normal kidney function and ESKD patients undergoing haemodialysis with current dosing recommendations.
conclusionWe successfully expanded a general-purpose model to reflect the piperacillin/tazobactam pharmacokinetics in ESKD patients undergoing intermittent haemodialysis using high-flux dialysers. The current dosing recommendations provide inconsistent probability of target attainment in ESKD patients compared with the general population.
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