This document discusses several physiological factors that can affect drug absorption in the gastrointestinal tract. It covers topics like gastric emptying, intestinal transit, GI pH, blood flow to the GIT, and diseases of the GI tract, liver, and cardiovascular system. It also discusses how the contents of the GI tract like food, drugs, and enzymes can impact drug absorption through mechanisms like drug interactions, adsorption, complexation, and first-pass metabolism.

1. PHARMACEUTICS-
IV
(PHT 439 )
SALMAN BIN ABDUL AZIZ UNIVERSITY
COLLEGE OF PHARMACY
Physiological factors affecting Drug
Absorption

2. Physiology of GIT
GIT comprises of no. of components,
Stomach
Small Intestine
Large Intestine
The primary functions of GIT are
Secretion
Digestion
Absorption.

3. Physiological factors
1.Age
2.Gastric Empting
3.Intestinal
Transit
4.GI pH
5.Blood Flow to
GIT
6.Diseased State
7.GI Content
8.First pass effect

4. 1. Age
•In infants GI pH is high and intestinal
surface and blood flow to GIT is low as
compared to adults results in poor drug
absorption.
•In elderly people, alteration in drug
absorption becuase of alteration in
gastric emptying, and incidents of
achlorhydria and bacterial over growth in
small intestine.

5. 2. Gastric emptying
*Defined, as passage of contents of stomach
into the intestine.
*Rapid gastric emptying is advisable where:
•Rapid onset action is required, eg; sedatives.
•Dissolution of drug occurs in intestine eg;
Enteric coated tablets.
•Drug is unstable in gastric fluids.
•Drug is best absorbed from distal part of
small intestine, eg vitamin B 12 .

6. Kinetics of GI emptying
GI emptying is first-order kinetics many
parameters are used to quantify a gastric
emptying;
1. Gastric emptying rate: Is the speed at which
the stomach contents are emptied into the
intestine.
2. Gastric emptying time: Time required for
the GI content to empty into small intestine.
3. G.E.t1/2: Is time taken for half the stomach
contents to empty.

7. Factors affecting GI emptying
1.Volume of meals
2.Composition of meal
3.Physical state of meal
4.GI pH
5.Body posture
6.Emotional state
7.Exercise
8.Drugs

8. 1.Volume of meal: Larger the bulk of the meal, longer the
gastric time and however an initial rapid rate of emptying is
observed with large meal volume and initial lag phase in
emptying of small volume meals.
2.Composition of meal: The rate of gastric emptying for
various food materials in the following order
carbohydrates>proteins>fats.
3.Physical state: Liquid meal takes less time as compared
to solid meals.
4.GI ph: Gastric emptying is retarded at low stomach pH and
promoted at alkaline pH.

9. 5.Exercise: Vigorous physical training retards gastric
empting.
6.Body posture: Gastric emptying is favored while
standing and by lying on right side.
7. Emotional state: Stress and anxiety promotes GI
motility, where as depression retards it.
8.Drugs: That retards gastric emptying are
antacids, anti cholinergic, narcotic analgesics and tri
cyclic antidepressants.
And metoclopramide, domperidone and cisapride
stimulate gastric emptying.

10. 3. Intestinal transit
Defined as, the residence time of drug in small
intestine.
Delayed intestinal transit is desirable for:
1.Sustained release dosage forms,
2.Drug that only release in intestine ie ,enteric
coated formulations,
3.Drugs absorbed from specific sites in intestine,
eg; several B vitamins

11. 4. GASTROINTESTINAL pH
GI pH influence in several ways:
1.Disintegration: Disintegrating of some dosage
forms is pH sensitive, enteric coated tabs dissolve
only in alkaline pH.
2.Dissolution: A large no. of drugs either weak acids
or weak bases, their solubility is greatly affected by
GI pH.
-weakly acidic drugs dissolve rapidly in alkaline pH.
-basic drugs soluble in acidic pH..
3.Absorption: Depending upon drug pKa whether its
an acidic or basic drug the GI pH influences drug
absorption.

12. 5. Blood flow to GIT
GIT is extensively supplied by blood capillary,
about 28% of cardiac output is supplied to GIT
portion, most drug reach the systemic
circulation via blood only.
Any factor which affects blood flow to GIT may
also affect absorption.

13. 6. Disease state
Several disease state may influence the rate and
extent of drug absorption.
Three major classes of disease may influence
bioavailability of drug.
•GI diseases
•CVS disease
•HEPATIC disease

14. GI diseases
A. GI infections :
1.Celiac disease: (characterized by destruction of
villi and microvilli) abnormalities associated
with this disease are increase GI emptying
rate and GI permeability, alter intestinal drug
metabolism.
2.Crohn’s disease: alter gut transit time and
decreased gut surface area.
B. GI surgery:
Gastrectomy may cause drug dumping in
intestine, osmotic diarrhoea and reduce
intestinal transit time.

15. CVS diseases
In CVS diseases blood flow to GIT decrease,
causes decreased drug absorption.
Disorders like hepatic cirrhosis influences
bioavailability of drugs which under goes first
pass metabolism.
Hepatic diseases

16. 7. Gastro intestinal contents
1.Food- drug interaction: In general presence of
food either delay, reduce, increase or may not
affect absorption.
•Aspirin Delayed
•Penicillin's Decreased
•Griseofulvin Increased
•Methyldopa Unaffected
2.Interaction of drug with normal GI contents:
GIT contains no. of normal constituents such as
mucin, bile salts and enzymes, which influence
the drug absorption. Eg; Inhibitory action of bile
on GI motility.

17. 3.Drug-Drug interaction in the GIT:
Physico chemical drug- drug interaction:
Adsorption: Eg; anti diarrhial preparations
contains adsorbents like kaolin, prevents a
absorption of many drugs co-administered with
them.
Complexation: Eg; penicillin derivative with ca-
gluconate.
pH changes: Basic drugs changes gastric pH
Eg; tetracycline with antacids

18. 8. First pass metabolism
Four primary systems which affect pre systemic
metabolism of a drugs.
1. Luminal enzymes.
2. Gut wall enzymes or mucosal enzymes.
3. Bacterial enzymes.
4. Hepatic enzymes.

19. •Lumenal enzymes: These are enzymes present in gut fluids
and include enzymes from intestinal and pancreatic
secretions.
•Gut wall enzymes: Also called mucosal enzymes they are
present in gut and intestine, colon.
•Bacterial enzymes: GI microflora scantily present in stomach
and small intestine and is rich in colon.
•Hepatic enzyme: several drug undergo first-pass hepatic
metabolism, highly extracted ones being isoprenaline,
nitroglycerin, morphine etc.

20. Question ?