Individualized Dosing With High Inter-Occasion Variability Is Correctly Handled With Model-Informed Precision Dosing-Using Rifampicin as an Example.

ABSTRACT: Rifampicin exhibits complexities in its pharmacokinetics (PK), including high inter-occasion variability (IOV), which is challenging for dose individualization. Model-informed precision dosing (MIPD) can be used to optimize individual doses. In this simulation-based study we investigated the magnitude of IOV in rifampicin PK on an exposure level, the impact of not acknowledging IOV when performing MIPD, and the number of sampling occasions needed to forecast the dose. Subjects with drug-susceptible tuberculosis (TB) were simulated from a previously developed population PK model. To explore the magnitude of IOV, the area under the plasma concentration-time curve from time zero up to 24 h (AUC_0-24h) after 35 mg/kg in the typical individual was simulated for 1,000 sampling occasion

SUBMITTER: Keutzer L 

PROVIDER: S-EPMC7266983 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature