An In Silico Knockout Model for Gastrointestinal Absorption Using a Systems Pharmacology Approach - Development and Application for Ketones.

ABSTRACT: Gastrointestinal absorption and disposition of ketones is complex. Recent work describing the pharmacokinetics (PK) of d-β-hydroxybutyrate (BHB) following oral ingestion of a ketone monoester ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate) found multiple input sites, nonlinear disposition and feedback on endogenous production. In the current work, a human systems pharmacology model for gastrointestinal absorption and subsequent disposition of small molecules (monocarboxylic acids with molecular weight < 200 Da) was developed with an application to a ketone monoester. The systems model was developed by collating the information from the literature and knowledge gained from empirical population modelling of the clinical data. In silico knockout variants of this systems model were used to explore

SUBMITTER: Shivva V 

PROVIDER: S-EPMC5042539 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature