Chemistry Reference
In-Depth Information
Although
in silico
ADME/Tox predictions grow constantly as a viable alternative,
their success is still limited to cases where the query compounds are similar to
those with already characterized ADME/Tox properties [1, 3, 5, 6]. Despite these
drawbacks,
in silico
methods are in constant improvement aided by new
ADME/Tox variable studies. They are becoming a useful and viable tool in drug
development [7].
This chapter will focus primarily on absorption, metabolism and toxicity
predictions, focusing on the computational strategies, methods and commonly
used softwares to profile ADMET predictions and how could they be a useful tool
in drug design strategies.
ABSORPTION
Absorption is the process in which a drug enters the bloodstream without being
chemically altered in order to be available to reach its site of action in sufficient
quantity [8]. In order for a drug to perform a therapeutic effect, it has to be taken
to the bloodstream passing through various
in vivo
barriers such as the digestive
tract (intestinal absorption), and reach specific tissues or organs [9].
The possible routes for a drug entering the body are: a) enteral; b) parenteral and
c) topical. The enteral route includes processes in which the drug is administered
through the gastrointestinal tract by sublingual (drug placed under the tongue),
oral (swallowing the drug) and rectal (drug absorption occurs in the rectum) via.
Parenteral routes are administration routes of a drug that do not involve the digest
tract. In this route, drugs are administered by intravascular (drug administered
directly into the bloodstream), intramuscular (drug injected in skeletal muscle),
subcutaneous (drug absorption from subcutaneous tissue) injection and inhalation
(absorption through the lungs). Topical administration involves dosing for
mucous membranes (eye drops, antiseptic, sunscreen, for nasal passages,
etc
.) and
skin by dermal (oil or ointment - local action) and transdermal (drug absorption
through the skin - systemic action) route. Formulations of a drug can be
developed to increase the absorption of molecules and this is achieved by
increasing the solubility or dissolution rates of the drug product [10].
