orally administered drugs. Most orally administered drugs are absorbed
through the membranes of the GI tract. The rate of absorption will depend
mainly on the rate of dissolution of the dosage form, that is, the rate at which
the drug solid dosage forms passes into solution, the pH of the medium con-
taining the drug (see Section 2.7.1), the lipid–aqueous medium partition coeffi-
cient of the drug and the surface area of the absorbing region of the GI tract.
Drugs absorbed from the GI tract must pass through the GI tract membrane,
liver and other organs in order to reach the general circulation system. A
fraction of the drug will be lost by metabolism and excretion as it follows this
route to the circulatory system. These losses are referred to as thefirst pass effect
orfirst pass metabolism. Since the main areas of excretion and metabolism in the
systematic circulatory system are the enzyme-rich liver and lungs, the term is
usually taken to refer to the elimination of a drug by these two organs. However,
since the liver is the first organ the drug passes through after absorption from
the GI tract and it is also the principal area of metabolism, the effect of the lungs
is often ignored, and the term first pass metabolism is frequently used as though
it involved only the liver.
The physiology of drug absorption from the GI tract has a direct effect on the
bioavailability(F) of a drug. Bioavailability is defined as the fraction of the dose
of a drug that enters the general circulatory system, that is:
F¼
amount of drug that enters the general circulatory system
dose administered
(8:22)
Since the area under the plasma concentration–time curve (AUC) for a drug
is a measure of the total amount of a drug reaching the general circulatory
system, the bioavailability of a drug may also be defined in terms of the AUC
as:
F¼AUC=dose (8:23)
If all the dose of a drug reached the circulatory system, the bioavailability as
defined by Equation (8.22) would have a value of unity 1. Therefore, ifEis the
extraction for first pass metabolism,
F¼ 1 E (8:24)
and so, for orally administered drugs, Equation (8.24) approximates to:
F¼ 1 EH (8:25)
172 PHARMACOKINETICS