Page 231 - Academic Press Encyclopedia of Physical Science and Technology 3rd BioTechnology

P1: GTV/GWT P2: GRB/GJP QC: FYDFinal Pages
Encyclopedia of Physical Science and Technology EN011J-559 July 25, 2001 18:57

Pharmacokinetics 809

atively impermeable to the passive transfer of solutes and
water. Throughout the tract, there is a varying environment
of pH and composition.
In the oral cavity, the epithelium is relatively thin and
very well vascularized, so that it is potentially an excellent
site for absorption of weak electrolytes which would be
present in an undissociated form. The epithelium remains
moist with saliva, which maintains the pH in a slightly
acidic condition. However, the constant secretion and flow
of saliva tends to dilute any solution in the oral cavity
and move it toward the esophagus. Solid tablets can be
held under the tongue, and substances are rapidly absorbed
from the tablet into the blood. Nitroglycerin is an example
of a drug often administered via this route; it provides
rapid relief from chest pain due to poor perfusion of the
heart. Advantages of sublingual administration include
direct absorption into the general circulation, which does
not pass through the liver as it would if the drug were
FIGURE 5 Routes of administration; see text for a detailed dis-
absorbed in the stomach or intestines.
cussion of each route.
The stomach is the next major portal of entry of sub-
stances taken orally and swallowed. The rapid transit
II. DRUG ABSORPTION through the mouth and esophagus leaves little time for ab-
sorption in those regions. The makeup of the pill or capsule
Absorption of a drug consists in the movement of the sub- and how it is taken also determine the site of absorption.
stance from the site of administration to a body compart- If a tablet is taken with water on an empty stomach, it will
ment from which the drug has access to the target. Routes likely pass rapidly through the stomach and into the small
of administration (see Fig. 5) vary depending on whether intestine. On the other hand, if taken with food, the sub-
a local or systemic effect is desired. For example, a local stance will likely spend more time in the stomach. The
effect may be elicited by application of a drug to the skin surface of the stomach, called the gastric mucosa, is made
or a mucous membrane. The drug must have specific char- up of a series of infoldings which greatly increases the ab-
acteristics which limit its movement from the site of ad- sorptive surface area. The pH of the stomach is usually
ministration into the local target but not into the systemic quite low (pH < 3 in humans) and therefore substances
circulation. Administration into the gastrointestinal tract which are weak acids remain in undissociated form and
(sublingual, oral, or rectal route), inhalation into the lungs, are easily absorbed. Their rate of absorption will depend
or injection into the subcutaneous space, the muscle (in- on the lipid solubility.
tramuscular), or the cerebral spinal fluid (intrathecal) are The small intestine has extensive infoldings called villi;
examples of routes which will typically lead to systemic the villi are in turn lined by a brush border of microvilli.
effects. A substance is considered to be absorbed once it This hollow organ therefore presents a large absorptive
arrives in the blood circulation. Drugs administered orally surface for nutrients as well as for drugs. The passage
must transport across both epithelial and endothelial bar- of a substance through the small intestine normally takes
riers to reach the circulation; they may undergo binding several hours and absorption is usually complete. If the
within the tissue or uptake into cells and metabolism prior small intestine has been shortened through surgery or if the
to arrival at the blood capillary wall. The amount of a drug transit time has been decreased by diarrhea, then absorp-
absorbed systemically therefore depends on properties of tion may not be complete. The major mechanism of trans-
the drug and the characteristics of the barriers between the port is diffusion across the epithelium and subsequently
site of administration and the circulation. across the endothelium of vessels coursing through the
tissue. Drugs which are absorbed in this fashion enter
the intestinal circulation which flows to the liver via the
A. Gastrointestinal Absorption
portal vein. Therefore, drugs absorbed into the circula-
Thegastrointestinaltractincludestheoralcavity,thestom- tion of the hollow viscera pass through the liver prior
ach, the small intestines, the large intestine, and the rec- to reaching other organs. This event, which may result
tum. The entire system is lined with epithelial cells, which in metabolism of the drug, is designated a “first-pass ef-
typically have tight junctions between them which are rel- fect.” The first-pass effect may activate a drug, form active