Pharmacokinetics- Absorption 2

Question 1

What does drug absorption into the circulation generally require?

Answer 1

• Dissolved drug has to penetrate lipid membranes and epithelial barriers
• These may include epithelial lining of GI tract, endothelial lining of blood vessels or plasma membranes of target cells

Question 2

In what ways might drug penetration occur?

Answer 2

• Simple diffusion
• Facilitated diffusion
• Active transport
• Via aqueous pores or intracellular junctions

Question 3

How do lipid soluble drugs cross cell membranes?

Answer 3

Diffusion through lipid membrane

Question 4

How do water soluble cross cell membranes?

Answer 4

• Mol wt<200: diffusion through aquaporins

- Mol wt>200: diffusion through intercellular junctions

Question 5

How do water soluble molecules that resemble natural molecules cross the cell membrane?

Answer 5

• Via carrier
• Carrier molecule may facilitate diffusion of large, hydrophilic drug molecule down conc. gradient
• Or perhaps against conc. gradient by active transport

Question 6

What does Fick’s Law of Diffusion involve?

Answer 6

• Simple passive diffusion across a membrane depends on:

- Conc. gradient, Area, Thickness of membrane, Permeability of membrane to drug

Question 7

According to Fick’s Law how can diffusion be calculated

Answer 7

(C1-C2) x Area x Permeability / Thickness

Question 8

Describe how ionisation might affect movement across the membrane

Answer 8

• Some drugs are weak acids or bases and can exist as ionised or non-ionised
• Only non-ionised forms will diffuse across a lipid membrane

Question 9

What is bioavailability?

Answer 9

• The fraction of administered dose that reaches the general circulation unchanged
• Can be estimated from the area under a curve

Question 10

What affects oral bioavailability?

Answer 10

• Extent of drug solubility
• Extent of drug binding to gut contents
• Extent of drug degradation (e.g. in gut, liver)
• Extent of drug absorption