Considerations and Caveats when Applying Global Sensitivity Analysis Methods to Physiologically Based Pharmacokinetic Models.

ABSTRACT: Three global sensitivity analysis (GSA) methods (Morris, Sobol and extended Sobol) are applied to a minimal physiologically based PK (mPBPK) model using three model drugs given orally, namely quinidine, alprazolam, and midazolam. We investigated how correlations among input parameters affect the determination of the key parameters influencing pharmacokinetic (PK) properties of general interest, i.e., the maximal plasma concentration (C_max) time at which C_max is reached (T_max), and area under plasma concentration (AUC). The influential parameters determined by the Morris and Sobol methods (suitable for independent model parameters) were compared to those determined by the extended Sobol method (which considers model parameter correlations). For the three dru

SUBMITTER: Liu D 

PROVIDER: S-EPMC7367914 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature