drug absorption and bioavailability

Question 1

what are the routes of admin?

Answer 1

o Intravascular – placement of the drug directly into blood, this doesn’t have the absorption process as drug is directly placed into the blood. (intravenous (iv) or intra-arterial)
o Extravascular – oral, sublingual, subcutaneous, intramuscular, rectal. Absorption process is relevant.

Question 2

why is the site of action important?

Answer 2

• Drug should reach the site of action at a desired concentration – important for therapeutic effect

Question 3

what is the anatomical sequence of drug absorption?

Answer 3

o dissolves in gastrointestinal lumen  absorption across gut wall  liver  systemic circulation§

Question 4

what is bioavailability (F)?

Answer 4

• Bioavailability (F) refers to the extent of absorption of intact drug. Fraction of an extravascularly administered dose that reaches the systemic circulation intact

Question 5

what is F usually expressed as?

Answer 5

between 0-1 or as a %

Question 6

why do we need to know F/

Answer 6

o You need to know this value to make sure the dose you are giving is correct for the amount that will reach systemic circulation. Especially if it has a poor F

Question 7

what is absolute bioavailability?

Answer 7

• Absolute bioavailability is usually assessed with reference to an intravenous dose (gold standard – complete absorption)

Question 8

what is relative bioavailability?

Answer 8

• Relative bioavailability comparison of the bioavailability between formulations of a drug given either by the same or different routes of administration

Question 9

what is bioequivalence?

Answer 9

• Bioequivalence formulations containing the same dose of same chemical entity, generally in the same dosage form, intended to be interchangeable. This is usually important when a drug comes of patent

Question 10

what are the rate limiting steps for oral absorption?

Answer 10

A. Disintegration time and dissolution rate
B. Gastric emptying and intestinal transit
C. Movement through membranes
a) perfusion or
b) permeability limitations
D. First-pass metabolism in the gut/liver
There are several potential sites of loss – all may contribute to decrease in systemic absorption

Question 11

what is AUC?

Answer 11

area under plasma conc-time curve

Question 12

what is Cmax?

Answer 12

max plasma conc

Question 13

what happens if plasma conc-time profiles are similar?

Answer 13

less likely to cause clinically relevant differences in therapeutic and adverse effects!

Question 14

what factors affect intestinal absorption?

Answer 14

The small intestine is the MAJOR site of drug absorption after oral administration.
• Surface area
• Blood flow
• Permeability
All favourable for small intestine compared to stomach, even for acids (pH).

Question 15

what is the role of gastric emptying?

Answer 15

Gastric emptying controls the delivery of drug to small intestine and affects the rate of absorption
A small amount of drug may be absorbed in the stomach but it is a minor.
Factors affecting gastric emptying
1. Co-administration of another drug
2. Food
3. Age – delays gastric emptying

Question 16

what are the effects of drug emptying and absorption?

Answer 16

• Metoclopramide -  gastric emptying - reaches small intestine much faster
o Cmax>Cmax,control and TmaxTmax,control

Question 17

what is the effect of food on gastric emptying?

Answer 17

water on a empty stomach as this increase gastric emptying.
 Fasted – fast delivery to upper small intestine, no major difference between the particle sizes
 Fed
- delayed gastric emptying
- affects the rate of absorption
- difference between particle sizes
 Small intestine
- Food has NO effect on transit time in small intestine
- No difference between different particle sizes

Question 18

what are examples of enteric coating?

Answer 18

to be given on a fasted stomach

 Examples: omeprazole, erythromycin

Question 19

what are examples of poorly soluble drugs?

Answer 19

to be taken with food
 Griseofulvin
 Number of antiretroviral drugs – darunavir, ritonavir
 Certain cancer drugs - lapatinib

Question 20

what are the risks associated with raised BMI?

Answer 20

• increased CVD
• increased diabetes risk
• increase muscoskeletal disorders
• increased risk of some forms of cancer

Question 21

what are the consequences of gastric bypass surgery?

Answer 21

 Gastric bypass - reduction in surface area of stomach, pH changes
 Bypass of main areas of drug absorption – e.g., duodenum and the jejunum (~75cm bypassed)
 Limited information available on potential problems in drug absorption

Question 22

what is the affect of drug absorption from coeliac disease?

Answer 22

 Expression of intestinal CYP3A reduced on average to 15% of expression levels in healthy subjects

Question 23

what is the effect on drug absorption due to liver cirrhosis?

Answer 23

 reduced activity of many metabolic enzymes, extent depends on severity (Child-Pugh A-C)

Question 24

what are the effects on drug absorption due to chronic kidney disease?

Answer 24

 increase Gastric emptying time
 increase pH
 Expression of some CYP450 enzymes changed