Drug absorption and bioavailability

Question 1

What is bioavailability?

Answer 1

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

Question 2

What is absolute bioavailability?

Answer 2

is usually assessed with reference to an intravenous dose

Question 3

What is the relative bioavailability?

Answer 3

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

Question 4

What is bioequivalence?

Answer 4

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

Question 5

Parameters defining bioequivalence:

Answer 5

• AUC – area under plasma concentration-time curve
• Cmax- maximum plasma concentration
• If plasma concentration-time profiles are similar - less likely to cause clinically relevant differences in therapeutic and adverse effects!

Question 6

Rate limiting steps for oral absorption:

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

Answer 6

B. Gastric emptying and intestinal transit. Gastric emptying controls the delivery of drug to small intestine and affects the rate of absorption

Question 7

Factors affecting gastric emptying:

Answer 7

1. Co-administration of another drug
2. Food
3. Age

Question 8

What is the effect of food on gastric emptying (fed and fasted)

Answer 8

• Gastric emptying differs between fasted state and meals

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 9

What is the effect of food on drug absorption?

Answer 9

Enteric coated – to be given on fasted stomach
–> Examples: omeprazole, erythromycin

Poorly soluble drugs – to be taken with food

• Griseofulvin
• Number of antiretroviral drugs – darunavir, ritonavir
• Certain cancer drugs - lapatinib

Question 10

Risks associated with a raised BM?

Answer 10

↑ Cardiovascular disease
↑ Diabetes
↑ Muscoskeletal disorders
↑ Some forms of cancer

Question 11

Effects of gastric bypass surgery on drug absorption and F:

Answer 11

• 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 12

Effect of disease on drug absorption and first-pass metabolism:

Answer 12

Coeliac disease
–> Expression of intestinal CYP3A reduced on average to 15% of expression levels in healthy subjects

Liver cirrhosis
–> reduced activity of many metabolic enzymes, extent depends on severity (Child-Pugh A-C)

Chronic kidney disease

• -> Gastric emptying time
• -> increased pH
• -> Expression of some CYP450 enzymes changed