Drug Distribution

Question 1

Define Drug Distribution

Answer 1

Dispersion of a drug among fluids and tissues of the body

Question 2

Where does the drug go?

Answer 2

• Some will go to the extravascular space (adipose tissue and muscles)
• Drug moves fast into well-perfused areas
• Drug moves slower into less well-perfused areas

Question 3

What is first-order kinetics?

Answer 3

• A constant fraction of drug is removed (not constant amount)
• The time to remove the drug is independent of dose (if you increase [dose], the same fraction is removed)

Question 4

What is zero-order kinetics?

Answer 4

• Occurs when something is saturated - your enzymes and transporters can only work so fast
• A constant amount of drug is removed
• The bigger the dose, the longer the time to remove it
• As the dose decreases, there will be no saturation so will return to first-order
• Variation between individuals of saturation points

Question 5

How do you work out Volume of Distribution?

Answer 5

Total amount of drug / [plasma] = apparent volume of distribution (Vd)

e.g. 20mg IV dose / 2mg/L in plasma = 10L Vd (4L Vascular + 6L Extravascular)

Apparent vol is the volume in which you are dissolving the drug in, not the amount of blood in the body

Question 6

What is Vd?

Answer 6

Volume of Distribution

• indicates the extent of distribution for a drug
• Clinically important for adjusting dosage
• Influenced by lipid/water solubility/ binding
• if bound to protein - tends to stay in blood
• if lipophilic = will tend to move out

Question 7

What is plasma clearance?

Answer 7

The volume of plasma cleared of drug per time (ml/min)

• Clearance = rate of elimination / plasma [drug]
• Constant in 1st order reactions
• Calculated my measuring Area under curve / time

Question 8

What is bioavailability?

Answer 8

F = The fraction of drug in the circulation compared to the dose
For IV, F = 1
For oral F < 1 as some is absorbed in other places and eliminated

Question 9

How do you choose a delivery route?

Answer 9

• Bioavalability
• Chemical properties of drug
• Convenience
• Desired onset/duration
• Specificity of action

Question 10

What is steady state?

Answer 10

The overall intake of a drug is in dynamic equilibrium with its elimination.
- Repeated doses of drug eventually produce a steady state concentration (after about 4/5 half-lives of a drug after regular dosing is started)

Question 11

Distribution summary

Answer 11

• [Drug] in circulation depends on ADME processes
• Therapeutic drugs follow first-order kinetics and sometimes zero-order
• Pharamcokinetics parameters (F, Vd, CL, half-life) describe how the body handles the drug after administration
• Steady state requires 4-5 half lives - also consider dosage frequently and variations in [drug]