Drug Distibution

Question 1

What is the aim of Multiple-dose therapy?

What is First Order Kinetics?

What is Zero Order Kinetics?

What is Mixed Kinetics?

Why can drugs accumulate very quickly?

Answer 1

• Keep concentrations as stable as possible
• Constant FRACTION of drug removed; time taken to remove drug is independent of the dose
• Constant AMOUNT of drug removed; the bigger the dose, the longer the time taken to remove it
• First order kinetics resumes when concentration decreases below the saturation point
• Limited enzymes and transporters in liver/kidney

Question 2

Volume of Distribution:
What is the equation?

What is it influenced by?

What is it’s clinical importance?

Answer 2

• Total amount of drug/[Drug] in plasma
• Lipid/water solubility, Binding to plasma proteins
• For adjusting the dosage

Question 3

Elimination:
What does it show?

What is Plasma Clearance (CL)?
→ What is the equation?

How does CL change with Half-life?
→ How is it shown on a kinetics graph?

Answer 3

• The activity of metabolising enzymes/excretion mechanisms
• Volume of plasma cleared of a drug over time (ml/min)
  → Plasma clearance = Rate of elimination/[Drug] in plasma
• ↑CL = ↓Half-life
  → Is the area under kinetics graph

Question 4

Bioavailability (F):
What is it? What does it measure?

How is it calculated?

What causes low bioavailability?

Answer 4

• Fraction of drug in circulation compared to dose; measures extent of Absorption
• By measuring area under Oral/IV dose graph
• Poor absorption, Chemical reactions at site of delivery, First-pass metabolism

Question 5

What is the Steady State of a dosing regimen?

Answer 5

• Repeated doses of drug eventually produce a steady state plateau concentration
• Fluctuation size is inversely proportional to number of daily doses
• If drug has a long half-life, you can achieve a steady state by a loading dose