Simulation-based evaluation of the impact of dose fractionation study design on antibiotic PKPD analyses.

ABSTRACT:

Objectives

To evaluate the impact of antibiotic dose fractionation study design on pharmacokinetic/pharmacodynamic (PK/PD) indices and PKPD model estimation.

Methods

PKPD models for meropenem and polymyxin B (PMB) were applied to (i) simulate various dose fractionation studies in mice to derive PK/PD indices and efficacy targets and (ii) perform stochastic simulations and estimations evaluating which efficacy assessment times, in addition to 24 h, would improve the estimation of drug effect parameters.

Results

The R ² values of PK/PD indices were primarily influenced by reductions of the dosing intervals for meropenem and by decreases of the lowest total daily dose for PMB. For certain study designs (e.g. frequent administration of higher meropenem d

SUBMITTER: Saporta R 

PROVIDER: S-EPMC11986329 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature