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6 Sep 2016

At the end of the session, the student should be able to:


Describe the physiology of GIT
Define rate-limiting step
Identify physiological factors that affect drug absorption
Describe the transit of pharmaceuticals in the GIT

Louie Fernand D. Legaspi, RPh


Instructor, DLSHSI

For drug with very poor aqueous solubility, the rate at which it

dissolves in the GI fluids is _________.


Rate-limiting step
Slowest step
Controls the overall
rate and extent of
drug absorption
Varies from drug to
drug

Rate limiting step: ______________.

For drug that has high aqueous solubility, its dissolution is

_______.
Rate limiting step: __________ (drug crosses the GI membrane)

The rate of release of drug from the dosage form (i.e. controlled-release

dosage form)

Solubility

The rate at which the stomach empties the drug into the small intestine

Permeability

The rate at which the drug is metabolized by enzymes in the mucosal

cells
The rate of metabolism during its initial passage through the liver.

6 Sep 2016

Cross-section through GIT

Links the oral cavity with

stomach.
Thick, 250 mm long and 20 mm

in diameter
Contains squamous epithelium of

non-proliferative cells.
Secrete mucus into lumen to

lubricate food and protect the lower


part from gastric acid.

pH 5-6
Rapid transit of dosage forms,

2 major functions:
to act as a temporary
reservoir for ingested food
and to deliver it to the
duodenum at a controlled
rate;
to reduce ingested solids to
a uniform creamy
consistency, by the action
of acid and enzymatic
digestion.

usually 10-14 sec

6 Sep 2016

Capacity: apprx 1.5L


<50 mL (fasted state)

Acid secreted by the parietal cells


(pH 1-3.5)
Gastrin (potent stimulator of gastric
acid production)
Pepsin (pepsinogen) breaks down
proteins to peptides at low pH.
pH>5, pepsin is denatured.
Mucus secreted by mucosal cells
and lines the gastric mucosa.

Longest (4-5 m) and most

convoluted part of GIT.


Functions:
Digestion (enzymatic
digestion begins in the
stomach and completed in
the small intestine)
Absorption

Rate of gastric emptying: can be

controlling factor in the onset of


absorption.

Parts:
Duodenum (200-300
mm)
Jejunum (2 m)
Ileum (3 m)

Has rich network of

both blood, lymphatic


vessels and lacteals
Surface area
Increased (600x), thus,
good absorption site

Folds of Kerckring
Villi: finger-like projections into

the lumen (apprx 0.5-1.5 mm


and 0.1 mm in diameter)
Microvilli: (apprx 600-1000) of

these brush-like structures


cover each villus, providing
largest increase in surface
area.
Covered by glycocalyx

6 Sep 2016

pH 6-7.5

Apprx 1.5 m

Secretions:
Brunners glands (duodenum):
bicarbonate
Intestinal cells: mucus and enzymes
Pancreatic secretions: NaHCO3
and enzymes (proteases, principally
trypsin, chymotrypsin &
carboxypeptidases, lipase,
amylases)
Bile: secreted by hepatocytes in the
liver into bile canaliculi,
concentrated in the gallbladder and
hepatic biliary system.

Functions
Absorption of Na+, Cl-, and
H2) from the lumen in
exchange for HCO3 and K
ions.
Storage and compaction of
feces.
pH 6-6.5 to 7-7.5

Gastric emptying
Small Intestinal transit
Colonic transit

The time a dosage form takes to traverse the stomach


Aka gastric residence time, gastric emptying time or gastric emptying

rate.
Highly variable and is dependent on the dosage form and the fed/fasted state of the

stomach.

Generally, drugs are between absorbed in the small intestine than in the

stomach, therefore increasing the rate of stomach emptying will promote


drug absorption
The quicker the stomach emptying, the ______ the plasma concentration
Slow stomach emptying increases degradation of drugs in the stomachs lower pH

Usually range between 5 min and 2 hours, to 12 hours


Fasted state: Interdigestive myoelectric cycle or migrating myoelectirc complex

(MMC) the electrical activity in the stomach that governs transit of dosage form.

6 Sep 2016

The time of transit between the stomach and the caecum


Factor

Increase

Decrease

Volume

Large volume
(initial)

Bulky materials [as compared


to small particles 9<1mm)]

Type of meal

Warm food

Fatty food, carbohydrate, col


dbeverages

Body position

Standing, supine

Lying (specially on the left


side)

Drugs

Metoclopramide

Anticholinergics, narcotics,
analgesics, propantheline

Emotional
state

Aggression, stress

Depression

Exercise
Disease

Two main types of intestinal movement:


Propulsive: primarily determine the intestinal transit rate and hence the residence
time of the drug or dosage form in the small intestine
Mixing

After exercise
Hyperthyroidism

Parkinsons

Constant at around 3 hours

Varies between 2 and 48 hours

Important for dosage forms that release their drug slowly


Controlled- sustained- prolonged-release systems
Entericcoated dosage forms which release drug only hen they reach the small
intestine
Drugs that dissolve slowly in intestinal fluids
Drugs that are absorbed by intestinal carrier-mediated transport system