1. Surface area of the
gastrointestinal absorption sites:
The biological environments and the areas of membrane
available for absorption are the stomach, small intestine & large intestine.
The presence of
a. folds in the mucosa
b. villi &
c. microvilli are responsible for
absorption in the small intestine which having the largest surface area for
absorption i.e. the small intestine is the location of highest carrier density.
But some drugs such as
sulfasalazine absorbed in large intestine which degraded by bacterial flora in
this region before absorption therefore absorb from large intestine.
2. pH of gastrointestinal fluids:
The pH of the fluids varies along the length of
the GIT
pH in fasted state
•
Stomach
|
1→ 3.5
|
•
Small intestine
|
5→ 8
|
• Duodenum
|
5→ 6
|
•
Lower ileum
|
about 8
|
•
Large intestine
|
8
|
Gastric fluid pH generally increases when food is ingested
and then slowly decreases over the following few hours.
GI pH depending on such factors as:
1.
The general health of the individual
2.
The presence of localized disease condition (e.g. gastric & duodenal ulcer )
3.
The type &amount of food ingested
4.
Drug therapy e.g.
anticholinergic drugs →↓gastric secretion
&
antacid →↑ gastric pH for short time
pH is major influence on the
dissolution rate and hence the overall absorption rate of such drug
administered in a solid dosage form such as tablet or a hard gelatin capsule
3. Gastric emptying rate (GER)
Most drugs are absorbed from the small intestine
following peroral administration.
↑GER→ ↓ rate
at which drug in solution →↓rate of drug absorption → delay the onset of the
therapeutic response of the drug.
↓GER →chemical degradation in the stomach by low pH or
enzyme activity →conc.→↓ bioavailability.
·
Factors promoting GER include: hunger ,anxiety ,the patient's body
position (i.e. lying in the right side) the intake of liquids & antiemetic
drug (metoclopramide)
·
GER is retarded by factors such as fatty foods, a high bulk diet,
gastric ulcer, pyloric stenosis, the patient's body position (lying in the left
side) & drugs such as antichlinergics.
Note: unless a drug
is irritating to the gastric mucosa , a drug should not be administered with or
immediately after a bulky meal.
4.
Intestinal motility
The small intestine is
the primary site of drug absorption.
There are two types of
Intestinal movements,
a. Propulsive b.
Mixing
Determined
the ↑the area of contact between drug in
intestinal transit rate& solution& the GI membrane→
the residence time of ↑ absorption
a drug.
Note:
↑propulsive motility → ↓ residence time →↓dissolution →↓absorption.
Intestinal residence time (IRT) important for:
1.
dosage form which release drug slowly (e.g. sustained & prolonged
release dosage form)
2.
Enteric-coated dosage forms which release drug only when they reach the
small intestine
3.
Drugs which are absorbed by intestinal carrier-mediated transport
system.
5.
Presystemic
metabolisms
Drug may be chemical degraded &/or metabolized in
GIT
Mean incomplete bioavailability
Chemical degradation such as hydrolysis by effect of
pH or enzymes located in the intestinal mucosa e.g. erythromycin.
Many pro drugs such as erythromycin stearate &
chloramphenicol
palmitate depend on gradation in the GIT in order to
release the therapeutically active parent molecule.
v epatic
metabolism: first pass of absorbed drug through the liver may result in
metabolism of the drug intact
drug may never reach the systemic circulation this phenomenon is known as
the first pass effect and results in the a decrease bioavailability e.g. pethidine
6.
Influence of food and diet
The rate of absorption can be influenced by the
presence of food in GIT. Food may influence drug bioavailability by the
following mechanisms.
1.
Alteration in the rate of gastric emptying
2.
Competition between food component & drugs for absorption
3.
stimulation of GI secretions
↓Bioavailability or ↑ Bioavailability
(Degradation & formed complex) (↑ Dissolution by bile salt)
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