Chemistry Reference
In-Depth Information
favorably modeled, but the PBK model in rats gave a good fit as result for both
intravenous and oral dosing [20].
IDEA is another software tool from Lions Bioscience Inc. that acting like human
physiology and has models for intestinal permeability, solubility, surface area and
fluid movement. This approach for absorption module was based on simulations
models to predict oral drug absorption described by Grass [21]. According to this
work, they discuss that broad models for oral absorption have the potential to
provide substantial benefits to the discovery process and as a result, a significant
impact on the yield potential. These models allow direct extrapolation to humans
from data measured
in vivo
, thus IDEA makes an
in vitro
determination for the
estimation of ADME properties [21].
Parrot and Lavé [22] made an assessment of two software tools that apply
physiologically based models for prediction of intestinal absorption in human,
GastroPlus and IDEA. They were compared to predict oral absorption describing
a comparative evaluation and a discussion of the usability and functionality using,
for this purpose, a set of 28 drugs. For pure
in silico
prediction, in terms of ability,
both programs were around 70% correct classification rate (71% for IDEA and
68% for Gastroplus) into high (≥66%), medium (between 33-66%) and low
(≤33%) category of absorption, in other words, there was no significant difference
in performance between them. An improvement in predictive accuracy was
observed using IDEA for CACO-2 permeability, whereas GastroPlus did not
show any enhancement in predicting, independent of the
in silico
or experimental
permeability used.
Here the process was highlighted in which all drugs need to pass to be absorbed
and some progress
in silico
modeling of absorption and oral bioavailability. A
brief summary of the methodological point of view, as well as some advantages
and disadvantages of the programs used to predict human intestinal absorption has
been presented as well. Some variables can affect bioavailability and
consequently drug absorption such as site of drug absorption, membrane
transporters and presystemic drug metabolism. Although there are several
in silico
methods that can be useful in predicting absorption properties for drug design,
