Chemistry Reference
In-Depth Information
the more lipid-soluble species is the unionised free base, B, which will be
present to the greatest extent in solutions of high pH, such as are found in
the small intestine (pH range 6-8). The pH partition hypothesis predicts
that basic drugs (such as morphine, codeine, antihistamines, etc.) will be
absorbed into the body better from the small intestine than from the acidic
stomach, since the base will be predominantly unionised in the intestine,
rather than existing as the ionised conjugate acid in the stomach. This is
important for the patient, since, if a drug can only be absorbed from the
small intestine, there will inevitably be a delay in onset of action if the drug
is taken orally. The drug has to be swallowed and pass through the stomach
(where if it is basic it will exist predominantly in the ionised form) before
the stomach empties and the drug enters the small intestine and begins the
process of absorption. If, for example, a patient takes a basic drug such as
an antihistamine for travel sickness, they should be advised to swallow their
medication at least an hour before they set off on their journey to allow
time for the drug to reach the site of absorption and partition into the
bloodstream. An estimate of the extent to which a weak acid or base will be
ionised at any given pH can be made using the approximate 'rule of thumb'
introduced in Chapter 1 if the p
K
a
of the acid or base is known.
Limitations of the pH partition hypothesis
The pH partition hypothesis is very useful as a model to explain the extent
of drug absorption in the body, but it must be borne in mind that the model
has some limitations. As usual, the real-life situation is more complex than
this simple model suggests. The theory predicts that weak acids will prefer-
entially be absorbed from the stomach, and weak bases from the small
intestine but, in reality,
the vast majority of drugs are absorbed from the
small intestine irrespective of their degree of ionisation
. This is because the
small intestine has evolved as the organ where absorption of food (and
drugs) takes place. The small intestine has three sections, the
duodenum
, a
short curved section attached to the back wall of the abdomen, and the
jejunum
and
ileum
, two larger coiled segments that can move about within
the abdominal cavity. The existence of these three sections means that the
small intestine is long (about 6.5 metres in an adult) and has much higher
surface area (estimated as 100 m
2
) than the stomach. The large intestine,
which frames the coils of the small intestine, follows on from the small
intestine and is itself about 1.5 metres long. This means the total length of
the gut is over 8 metres, or approximately five to six times an individual's
height. The high surface area of the small intestine is achieved due to its
convoluted folded structure (see Figure 2.6), which is increased further by
