Mechanism-Based Modeling of Gastric Emptying Rate and Gallbladder Emptying in Response to Caloric Intake.

Bile acids released postprandially modify the rate and extent of absorption of lipophilic compounds. The present study aimed to predict gastric emptying (GE) rate and gallbladder emptying (GBE) patterns in response to caloric intake. A mechanism-based model for GE, cholecystokinin plasma concentrations, and GBE was developed on data from 33 patients with type 2 diabetes and 33 matched nondiabetic individuals who were administered various test drinks. A feedback action of the caloric content entering the proximal small intestine was identified for the rate of GE. The cholecystokinin concentrations were not predictive of GBE, and an alternative model linking the nutrients amount in the upper intestine to GBE was preferred. Relative to fats, the potency on GBE was 68% for proteins and 2.3% for carbohydrates. The model predictions were robust across a broad range of nutritional content and may potentially be used to predict postprandial changes in drug absorption.

AMGET, an R-Based Postprocessing Tool for ADAPT 5.

ADAPT 5 is a powerful modeling software for population pharmacokinetic and pharmacodynamic systems analysis, but provides limited built-in functionality for creating pre- and post-analysis diagnostic plots. ADAPT 5 Model Evaluation Graphical Toolkit (AMGET), an external package written in the open source R programming language, was developed specifically to support efficient postprocessing of ADAPT 5 runs, as well as NONMEM and S-ADAPT runs. Using interactive navigational menus, users of AMGET are able to rapidly create informative diagnostic plots enriched by the display of numerical and graphical elements with a high degree of customization using a simple settings spreadsheet. This article describes each feature of the AMGET package and illustrates how it allows users to utilize the powerful numerical routines of the ADAPT 5 package in a more efficient manner through the use of a simulated dataset and a simple pharmacokinetic model optimized using the maximum likelihood expectation maximization (MLEM) algorithm of ADAPT 5.CPT: Pharmacometrics & Systems Pharmacology (2013) 2, e61; doi:10.1038/psp.2013.36; published online 31 July 2013.