Absorption is the process of delivering a drug into the blood stream. Absorption
can be accomplished by administering the drug in a variety of different ways (e.g.
orally, rectally, intra-muscularly, subcutaneously, inhalation, topically, etc.). Note,
that if a drug is administered intravenously (placed directly into the blood stream),
the need for absorption is bypassed entirely.
For drug absorption to occur, a drug must cross biologic barriers (e.g.
epithelial/endothelial cells, etc.). Only a few drugs move across cellular barriers in
an “active” way; that is, a way that requires energy (ATP) and moves the drug from
an area of low concentration to an area of higher concentration. On the other
hand, most drugs cross cellular barriers via passive diffusion; that is, drugs simply
move from an area of higher concentration to an area of lower concentration by
diffusing through cell membranes. This type of drug movement does not require
any energy expenditure, but will be influenced by the size of the drug and the
solubility of the drug.
For drug absorption to be most efficient, the properties of the drug itself and the pH
of the environment where the drug is located must be considered. Most drugs are
either weak acids or weak bases. Drugs that are weak acids will pick up a proton
when placed in an acidic environment and will, thus, be un-ionized.
H+ + A- <-> HA
In the above example, when the weak acid, A-, is placed into an acidic
environment, H+; the drug picks up a proton and is no longer ionized (it becomes
protonated as HA). If the same acid, A-, is placed into an alkaline environment, OH, the drug will remain ionized, as A-.
Drugs that are un-ionized will be better able to diffuse through a lipid cellular
membrane, cross a biologic barrier, and enter the bloodstream (e.g. be absorbed)
compared to drugs that are ionized. Thus, a key take-home point is: a drug that is
a weak acid will be best absorbed in an acidic environment (because it gains a
proton and becomes un-ionized).
The opposite is true for drugs that are weak bases. Consider, a weak base, NH3. In
an acidic environment, H+, the drug gains a proton and becomes ionized.
H+ + NH3 <-> NH4+
On the other hand, in an alkaline environment, a drug that is a weak base would
remain un-ionized.
Thus, the take-home message, again, is that weakly basic drugs are more likely to
absorbed in alkaline environments where they remain un-ionized compared to
acidic environments where whey gain a proton and pick up a charge. Ionized (or
charged) drugs are not absorbed as efficiently as un-ionized drugs are. Practically
speaking, this means that if taken orally, a drug that is a weak acid will be
absorbed primarily in the acidic environment; whereas, a drug that is a weak base
will be absorbed in the alkaline environment small intestines.
Physiogically speaking, even though the stomach is acidic, it is not well-suited for
drug absorption, even for drugs that are weak acids due to its thick mucus layer
and relatively small surface area. The stomach is more of a “storage” organ than an
absorptive one. In contrast, the small intestines have a large surface area
available for absorption owing to extensive villi and microvilli. As a result, acidic
drugs are most likely to be absorbed in the acidic areas of the proximal duodenum;
whereas, basic drugs will be best absorbed in more alkaline areas of the distal
ileum.
In addition to a drug’s ionization status, a drug is more likely to be absorbed if it
contains lipophillic chemical groups, lacks bulky/oxygenated side chains, and is not
too large in size.
Other factors that also impact drug absorption include the following:
1. Physiologically, a drug’s absorption is enhanced if there is a large surface area
available for absorption (e.g. villi/microvilli of intestinal tract) and if there is a
large blood supply for the drug to move down its concentration gradient.
2. The presence of food/other medications in the stomach may impact drug
absorption – sometimes enhancing absorption and other times forming
insoluble complexes that are not absorbed (it depends on the specific drug).
3. Some drugs are inactivated before they can be absorbed by enzymes, acidity,
bacteria, etc.