Drug absorption and bioavailability

Question 1

What are the systemic routes for drug administration?

Answer 1

o Intravascular – placement of the drug directly into blood (intravenous (iv) or intra-arterial) (NO ABSORPTION)
o Extravascular – oral, sublingual, subcutaneous, intramuscular, rectal (ABSORPTION NECESSARY)

Question 2

What can occur if locally administered drugs (e.g. creams) are absorbed systemically?

Answer 2

Undesired effects/side effects

Question 3

What absorption pathway does a drug take after oral administration?

Answer 3

• dissolves in gastrointestinal lumen
• absorption across gut wall
• liver
• systemic circulation

Question 4

What is the bio-availability (F) value ?

Answer 4

Between 0 and 1 or expressed in %

Question 5

What is absolute bioavailability?

Answer 5

is usually assessed with reference to an intravenous dose

Question 6

What is relative bioavailability?

Answer 6

Comparison of the bioavailability between formulations of a drug given either by the same or different routes of administration

Question 7

What is bioequivalence?

Answer 7

Formulations containing the same dose of same chemical entity, generally in the same dosage form, intended to be interchangeable

Question 8

What are the rate limiting steps for oral absorption?

Answer 8

1. Disintegration time and dissolution rate
2. Gastric emptying and intestinal transit
3. Movement through membranes
   a. Perfusion or
   b. Permeability limitations
4. First pass metabolism in the gut/liver

Question 9

What factors affect intestinal absorption?

Answer 9

o Large SA
o Villi and microvilli
o One layer of Epithelial cells – thin for molecules to pass
o Good blood supply

Question 10

What is the role of gastric emptying in drug absorption?

Answer 10

Gastric emptying controls the delivery of drug to small intestine and affects the rate of absorption

Question 11

What factors affect gastric emptying?

Answer 11

o Co-administration of another drug
o Food
o Age – delays gastric emptying, changes in physiology

Question 12

What effects would a drug that enhances gastric emptying have on another drug taken at the same time?

Answer 12

Drug would reach the small intestine much faster and therefore absorbed faster. Cmax and Tmax would also be higher (shifted to the left)

Question 13

What is the effect of food on gastric emptying?

Answer 13

• 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
(although the RATE is slower, the AMOUNT of drug absorbed is still the same - just takes longer)

Question 14

How should enteric coated drugs be taken?

Answer 14

To be given on fasted stomach to avoid coating getting damaged

Question 15

What can be done to improve absorption of poorly soluble drugs?

Answer 15

Take with food

Question 16

What are the effects of gastric bypass surgery on drug absorption and F?

Answer 16

• 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
o Reports of both increased and decreased F

Question 17

What is the effect of Coeliac disease on drug absorption and first pass metabolism?

Answer 17

o Expression of intestinal CYP3A reduced on average to 15% of expression levels in healthy subjects
o Limited data on the effect of disease on other drug metabolising enzymes

Question 18

What is the effect of liver cirrhosis on drug absorption and first pass metabolism?

Answer 18

o Reduced activity of many metabolic enzymes, extent depends on severity (Child-Pugh-A-C)
o C is more severe
o Intestinal enzymes may be effected as a result

Question 19

What is the effect of CKD on drug absorption and first pass metabolism?

Answer 19

o Increased gastric emptying time
o Reduced renal
o Increased pH
o Expression of some CYP450 enzymes changed