Chemistry Reference
In-Depth Information
often used to as a tool to identify parameters that could potentially enhance the
bioavailability of a compound as well. Some mechanisms are implemented in
GastroPlus like gastrointestinal simulation technology (GIST), and Advanced
Compartmental Absorption Transit (ACAT) model based upon an original CAT
model first elucidated by Yu
et al.
[18], this method is based on nine compartments
comparable to the different portion of the digestive tract, among them are seven
compartments of the small intestine and colon. Kocic and coworkers [19] reported
that the GIST model was used to give a close prediction of LT4 oral absorption.
Levothryroxine (LT4) is a drug orally administered used as alternate therapy in
primary hypothyroidism. The simulated studies were comparable with the data
observed in the
in vivo
bioequivalence study, thus demonstrating that the GIST
model gives an accurate indicator of LT4 oral absorption.
Table 1:
Programs for
in silico
predictions of human intestinal absorption
Software
Purpose and/or function
Simulates gastrointestinal absorption and pharmacokinetics for drugs
administered orally or intravenously in human and animals. Makes
predictions of the first-passage effect in the gut and liver and plasma
concentration-time profiles. As well as simulations and predictions of
bioavailability and pharmacodynamics.
GastroPlus
(Simulation-
plus, Inc.
http://www.simulation-
plus.com)
Simulates human physiology and explains regional variations in intestinal
permeability, solubility, surface area and fluid motion. Absorption module
predicts the fraction dose absorbed over time, mass absorbed, soluble
mass, insoluble mass, absorption rate and intestinal drug concentration.
iDEA
(LionBioscience,
Inc. http://www.lion-
bioscience.com/)
To model the absorption of a lipophilic BCS (biopharmaceutical classification
system) Class II compound metabolized by CYP3A4 which may be administered
as a nanosuspension formulation, Gastroplus software program was used to study
the absorption attributes of the compound using the Advanced Compartmental
Absorption Transit (ACAT) model implemented in Gastroplus. In this case, the
program was used for building and optimizing the PBPK (Physiologically Based
Modeling) model to predict the rate and oral absorption in rats by modeling the
absorption of nanosuspension. The disadvantage of using GastroPlus for this
approach was that the absorption of the nanosuspension formulation could not be
