Biopharmaceutics Lecture 2

Question 1

Name the likely sites of drug absorption in the GIT

Answer 1

Small intestine
Mouth/cheeks
Stomach

Question 2

Describe how drug absorption occurs in the small intestine

Answer 2

Large surface area ~100m2 due to folds, villi, microvilli
Large blood supply
Nutrient transporters
Paracellular transport
Transcellular transport

Question 3

Describe the GIT in terms of a site of drug absorption compared to skin

Answer 3

More permeable surface than skin
But epithelial layer still acts as a barrier
Conceptually an internal tube with varying properties along its length

Question 4

The partition coefficient, P=

Answer 4

Concentration of unionised drug in the organic layer/concentration of unionised drug in the aqueous layer

Question 5

Describe the stomach as a likely site of drug absorpton

Answer 5

Low surface area, no folds, no villi
Tight junctions - paracellular transport
No transporters for nutrient absorption, hence very little absorption here but a few partial exceptions!

Question 6

What are the partial exceptions to the rule about drug absorption from the stomach?

Answer 6

Exceptions:

• very highly permeable drugs, e.g. Ethanol
• weak acids e.g. Aspirin

Question 7

Why is there little drug absorption in the stomach?

Answer 7

Gastric absorption occurs, but is much less than the rate of intestinal absorption. For most molecules, you can assume there is no gastric absorption.

Question 8

Describe how the mouth and cheeks act as a site for drug absorption. Name some drugs delivered this way

Answer 8

Convenient, fast (minutes) absorption
Avoid 1st pass metabolism by the liver
Appropriate for lipophilic drugs with a low Mr e.g. GTN, Midazolam

Question 9

Name 4 major ways GI absorption of drugs occurs

Answer 9

Transcellular
Paracellular
Carrier-mediated
Transcytosis

Question 10

Describe paracellular drug absorption

Answer 10

Small amount of drug absorbed this way, via gaps between the epithelial lining
Low Mr hydrophilic drugs enter this way
Drugs with LogP<0 can go via this route

Question 11

Describe transcellular drug absorption

Answer 11

Drugs that obey Lipinkski’s rules go this way
Via lipid bilayer of epithelial cells lining the GI lumen (most of the surface area)
Small, lipophilic, unionised drugs travel via diffusion across epithelial layer and into the blood

Question 12

Describe the role of specific carrier systems in drug absorption

Answer 12

Specific carrier systems (e.g. Amino acid uptake occurs this way) allow certain molecules in to cells
Saturation of these carrier systems can be an issue, which gives the pattern on non-linear bioavailability

Question 13

Describe the physiological factors of the mouth that produce variability in absorption across the GIT
State the transit time

Answer 13

Saliva - mild pH

Transit time - minutes

Question 14

Describe the physiological factors of the oesphagus that produce variability in absorption across the GIT

Answer 14

pH 5-6

Thick, muscular, low surface area

Question 15

Describe the physiological factors of the stomach that produce variability in absorption across the GIT
State the transit time

Answer 15

Volume alters 
50mL (fasted) - >1000mL (fed)
Acidic pH 1-3.5
Protease enzymes present to degrade pepsin
Smooth (no folds)
Mucus layer
Transit time 5minutes-2hours

Question 16

Describe the physiological factors of the small intestine that produce variability in absorption across the GIT
State the transit time

Answer 16

Very big surface area
Not sensitive to dosage form or fed/fasted state
The pH has a gradual increase from 5 (duodenum) to ~7.5 (ileum)
Large blood spply
Nutrient transporters
Paracellular transport
Bile and digestive enzymes present (lipase, amylase, trypsin)
Transit time 3-4 hours

Question 17

Describe the physiological factors of the colon that produce variability in absorption across the GIT
State the transit time

Answer 17

Large surface area
Ion transporters, water movement 
Caecum pH 6-6.5 
Towards rectum pH is 7-7.5 
Commensal bacteria present 
Transit time: 2-48 hours

Question 18

Describe the pattern of the nutrient transporter process when saturated

Answer 18

Passive process - linear

But if transporter saturation occurs, it produces variable bioavailability and becomes an active process (non-linear)

Question 19

What is the splanchnic circulation?

Answer 19

The circulation of the:
Stomach (gastric)
Small intestine
Colon 
Pancreas
Liver (hepatic)
Spleen (splenic)

Question 20

What is first pass metabolism? How does it happen?

Answer 20

First pass metabolism is a phenomenon of drug metabolism whereby the concentration of drug is greatly reduced before it reaches the systemic circulation.
It happens via:
From the intestinal veins, drug filters through the liver and is filtered through the hepatic sinuses

Question 21

% of cardiac output taken up by the splanchnic circulation

Answer 21

25%