Chemistry Reference
In-Depth Information
The most convenient way for patients to receive medications is by the oral route.
For a drug orally administered, a high and stable bioavailability is crucial for its
successful development. When the drug is orally administered it has to be
absorbed through the epithelium of the small intestine [11]. In this case, the drug
has to cross several membranes and barriers before reaching its primary site of
action. In this process some major factors that affect the absorption are involved,
such as the chemical degradation and metabolism of the drug in the
gastrointestinal tract and the efflux by P-gp transmembrane transporters [8].
The oral absorption computational prediction area has received concentrated
efforts since the oral bioavailability is one of the most desirable attributes of a
new drug and the first step to achieve oral bioavailability is to get a good oral
absorption [12]. This prediction is very challenging due to the fact that the
bioavailability is a complex function of many biological and physicochemical
factors [13].
The bioavailability (%F) itself is used to describe the degree to which a drug or
other substance becomes available to the target tissue after its administration.
When a drug is administered intravenously its bioavailability is 100%. However,
when a drug is administered by other routes (such as orally), its bioavailability
(oral bioavailability) is usually less than 100% due to degradation or metabolism
of the drug prior to absorption, incomplete absorption and first-pass metabolism
(first-pass clearance or presystemic metabolism). Before the drug reaches the
general circulation, first-pass metabolism clears the absorbed drug, thereby
becoming one of several other factors that limit bioavailability. A drug only has
oral bioavailability if it can reach the systemic circulation not only flowing
through the intestine, but also through the liver because drugs that are orally
administered must pass through the liver before reaching the general circulation
and some of these compounds are strongly metabolized through the liver (first-
pass effect) [13].
During the absorption process a fraction of the drug is lost; such loss is closely
related to the liver (metabolic, biliary) and intestine wall by liver cells or
enzymatic hydrolysis reactions (intestinal metabolism), respectively. Another
enzymatic reaction takes place in the plasma by hydrolytic enzymes in the blood
