2. Pharmacokinetics 1

Question 1

What is bioavailability (F)? How is this calculated?

Answer 1

F = fraction of a dose that enters a body compartment, usually circulation.

For IV drug, F = 100%. For oral route, F = AUCoral/AUCiv

Question 2

Suggest examples of passive and active factors that can affect uptake and oral bioavailability of a drug/

Answer 2

Passive:

• lipophilicity
• molecular size
• pH
• ionic charge
• pharmaceutical preparation/drug formulation (immediate release/modified release)

Active:

• 1st pass metabolism
• gut motility, vomiting, malabsorption, etc.
• presence of active transport systems
• splanchnic blood flow (reduced in shock and heart failure)
• drug destruction by gut and/or bacterial enzymes

Question 3

What is 1st pass metabolism? Give examples.

Answer 3

Any metabolism occurring before the drugs enters systemic circulation. Can occur in:

1. gut lumen
   - gastric acid, proteolytic enzymes, grapefruit juice
2. gut wall
   - P-glycoprotein pumps drugs out of intestinal enterocytes back into lumen
3. liver
   - e.g. propanolol, morphine extensively inactivated in liver

Question 4

Name the 2 main factors affecting drug distribution.

Answer 4

1. protein binding, e.g. albumin (acidic drugs), globulins (hormones), lipoproteins (basic drugs), acid glycoproteins (basic drugs)
2. volume of distribution - measure of how widely a drug is distributed in body tissues

Question 5

Suggest factors that might affect drug protein binding.

Answer 5

• hypoalbuminaemia
• pregnancy (changed fluid balance)
• renal failure
• DDIs

Question 6

Suggest factors affecting volume of distribution

Answer 6

• no. or specific receptor sites in tissues
• regional blood flow
• lipid solubility
• active transport
• disease states
• drug interactions