Pharmacokinetics

Question 1

Describe the key PK parameters.

Answer 1

• Clearance (L/h)
• Volume of distribution (L, L/kg)
• Half life (h)
• Cmax (ug/mL)
• Tmax (h)
• AUC0-X (ug.h/mL)
• Bioavailability (%)

Question 2

How do you calculate Drug Clearance?

Answer 2

Clearance = Dose / Area under curve (AUC)

Elimination rate (mg/h) = Cl total(L/h) x [Drug]plasma (mg/L)

Question 3

Define Volume of Distribution

Answer 3

The amount of drug in the body compared to the amount of drug in the blood plasma.

Question 4

Define Vd.

Answer 4

Volume distributed
- Drugs with high lipophilicity are able to traverse membranes
o Apparent Vd > 5 L
- Hydrophilic drugs are trapped in the plasma
o Apparent Vd approx. 3 L (plasma water)

Question 5

Define Half-life.

Answer 5

Time to halve drug amount in the body.

Question 6

Define Cmax and Tmax

Answer 6

Tmax = time taken to reach peak [plasma]
Cmax = peak plasma concentration

Question 7

Define Bioavailability

Answer 7

Difference between plasma concentrations following single oral dose and single IV dose of same amount
- Expressed as %

Question 8

Explain how Pharmacokinetics is useful in drug development and drug safety.

Answer 8

Pharmacokinetic analysis reveals the potential toxicity of new agents and therapeutic windows of a drug.

Therapeutic window: plasma concentrations above the [lowest effective] and below the [toxic]

Question 9

What is the most parsimonious model for graphing drug distribution?

Answer 9

Two-Compartmental Model

• Drug does not always distribute instantaneously throughout the body
• May distribute unevenly through tissues
• Peripheral compartments composed of tissues with lower perfusion or affinity
• Drugs may bind to tissue types such as melanin or DNA, or other