A quick slide

1. PHYSIOLOGICAL FACTORS
AFFECTING DRUG ABSORPTION
Presented by..
Bibek khatri
Binod sah
B.Pharma 17th
batch

2. INTRODUCTION

3. Basic consideration…
* Drug absorption is the process of movement of unchanged
drug from the site of administration to systemic
circulation.
*The main role of GIT is secretion, digestion,and absorption.
*The primary site for drug absorption is small intestine.
*The main role of large intestine is absorption of water and
electrolytes.
*the blood flow is high in small intestine(1lt/min) which is followed
by stomach(0.15lt/min) and large intestine(0.02lt/min).
*The surface area of small intestine is largest (200 square m)
stomach(0.1-0.25 square m) , large intestine(0.15 square m).

4. Physiological factors affecting drug
absorption are listed below:
1) Age
2)Gastric emptying time
3)Intestinal transit time
4)Gastro-intestinal pH
5)Disease states
6)Blood flow through the GIT
7)Contact time with gastro-intestinal mucosa
8)Gastro-intestinal contents
9)Presystemic metabolism.

5. 1)Age:
*In infants, the gastric pH is high and intestinal
surface and blood flow to the GIT is low
resulting in altered absorption pattern in
compare to adults.
*In elderly persons, gastric emptying altered ,
decreased intestinal surface area and GI blood
flow , higher incidents of achlorhydria so
impaired drug absorption.

6. 2) Gastric emptying :
• The process by which food leaves the stomach
and enters the duodenum.
• Since the intestine is major site of drug
absorption , rapid gastric emptying increases the
bioavailibility of the drug
• Rapid gastric emptying is required when the drug
is best absorbed from distal part of the small
intestine.

7. • Delayed gastric emptying is required when
drugs are absorbed from proximal part of the
small intestine and prolonged drug absorption
site contact is desired.
• Gastric emptying is a first order process.

8. Factors influencing gastric emptying
are..
Volume of meal As the volume of meal increases then
initially an increase and then decrease.
Type of meal Gastric emptying rate
carbohydrate>protein>fats
Temperature of the meal High or low temperature of meal reduce
the gastric emptying rate as compared to
temperature of the body.
Body posture Standing and lying on right side promotes
the gastric emptying while lying on left
side retards it.
Emotional state Anxiety and stress promotes gastric
emptying while depression retards it.
Exercise Vigorous physical training retards gastric
emptying

9. Disease states Disease like gastric ulcer , pyloric
stenosis diabetes retards gastric
emptying while partial or total
gastrectomy duodenal ulcer promotes
gastric emptying.
Drugs Drugs retarding gastric emptying are
antacid(aluminium hydroxide),
anticholinergics like atropine,
propantheline , narcotic
analgesic(morphine).
Drugs like metoclopromide ,
domperidone stimulate gastric emptying.

10. • Gastric emptying rate: This is the speed at
which the stomach contents empty into the
intestine.
• Gastric emptying time: Which is the time
required for the gastric contents to the small
intestine.
• Gastric emptying half-life: which is the time
taken for half the stomach contents to empty.

11. 3)Intestinal transit :
• Intestinal transit time is the major site of
absorption of most of drugs.
• The mixing movement of the intestine that
occurs due to peristaltic contractions
promotes drug absorption, firstly, by
increasing the drug intestinal membrane
contact and secondly by enhancing drug
dissolution of especially of poorly soluble
drugs,through induced agitation.

12. • Delayed intestinal transit is desirable for
A)Drugs that dissolve or release slowly from
their dosage form (sustained release
products) for eg. Chlorothiazide.
B)Drugs that dissolve only in intestine(enteric
coated formulations)
C)Drugs absorbed from specific sites in the
intestine (several B vitamins , lithium
carbonate etc.)

14. 4) Gastro-intestinal pH
• GI pH generally increases gradually as moves
down the stomach to the colon and rectum.
• GI fluid pH influence drug absorption in several
ways:
a) Disintegration:
the disintegration of some
dosage form is pH sensitive. With enteric coated
formulation, the coat dissolve only in the
intestine followed by disintegration of tablet.

15. b) Dissolution :
pH that favors the formation of salt of the
drug enhances the dissolution of that drug, and hence
absorption.weakly acidic drugs dissolve rapidly in
alkaine pH of intestine while basic drugs dissolve in the
acidic pH of stomach.
c)Stablity :
GI pH also influences chemical stability of the
drug. The acidic stomach pH causes the degradation of
penicillin G and erythromycin that can be overcome by
preparing prodrugs of such drugs that do not degrade
in acidic pH. For.erythromycin estolate.

17. 5) Disease states:
a)Gastric disease (Achlorhydric patients):
* They may not have adequate productions of the
acids in the stomach;stomach HCl is essential for
solubilizing insoluble free bases.
* Many weak-base drugs that cannot form
soluble salts & remain undissolved therefore
unabsorbed.
Eg:Dapsone , ketoconazole etc.
*In this disease absorption of especially acid drugs
decreases.

18. b)Cardio-vascular diseases:
• Several changes associated with congestive
cardiac failure influence bio-availabaility of a
drug viz..,edema of the intestine , decreased
blood flow to the GIT and gastric emptying
rate and altered GI pH, secretions and
microbial flora.

19. 6) Blood flow through the GIT:
• High perfusion rate of GIT ensures that once
the drug has crossed the membrane , it is
rapidly removed from absorption site thus
maintaining the sink conditions and
concentration gradient for continued drug
absorption.

20. 7) Contact time with Gastro-intestinal
mucosa:
• Aborption of drug increases with increase
contact time with gastrointestinal mucosa and
vice- versa.

21. 8) Gastrointestinal contents:
• A number of GI contents can influence the drug
absorption is discussed below:
a) Food drug interaction:
Presence of food may either delay,reduce
increase or may not affect drug absorption.
*delayed absorption: aspirin , paracetamol.
*decresaed absorption: penicillin,levodopa.
*increased absorption: griseofulvin,dizepam.
*unaffected absorption:methyldopa.

22. b) Fluid volume :
• Large fluid volume results in better
dissolution, rapid gastric emptying and
enhanced absorption.
• Ex: erythromycin is better absorbed when
taken with a glass of water under fasting
condition than when taken with meals.

23. c) Interaction of the drugs with normal GI
contituents:
The GIT contains a number of normal
contituents such as mucin, bile salt which
influence drug absorption. Mucin retards
absorption of streptomycin and bile salt
increase the absoption of lipid soluble drug
like griseofulvin.

24. d) Drug- drug interaction In the GIT:
Antacid and mineral subtitutes containing
heavy metals such as Al,Ca,Fe or Zn retard the
absorption of tetracyclin through formation of
complexes.

25. 9) Presystemic metabolism:
• The loss of drugs through bio-transformation by
eliminating organs(liver and GIT) during the
passage to systemic circulation is called as first-
pass or pre-systemic metabolism.
• The four primary system which affect pre-
systemic metabolism of a drug are:
a)Luminal enzymes
b)Gut wall enzymes/mucosal enzymes
c)Bacterial enzymes
d)Hepatic enzymes