Pharmacokinetics

Question 1

What is the difference between excretion and clearance?

Answer 1

Excretion is how the drug is taken out of the body, clearance is the volume of plasma that has been cleared of the drug over time

Question 2

What does Vd tell you?

Answer 2

Vd is the apparent volume of distribution in L. It tells you how much plasma you’d need to account for the concentration

Question 3

What factors does Vd depend on?

Answer 3

Drug permeability across membranes, protein binding, accumulation in tissues and pH partition

Question 4

What are the Vds of heparin, ethanol and Chloroquine?

Answer 4

Heparin = 3.5L - therefore it only stays in the plasma
Ethanol = 41.5L - this is the total body water
Chloroquine = ~15,000L - it is highly lipid soluble, and so can easily move out of the plasma into fatty tissue

Question 5

What is the equation for Vd?

Answer 5

Vd = Dose (D) / [drug] plasma

As [drug]plasma is C0,
Vd = D/C0

C0 = initial concentration of the drug in the plasma (maximal dose)

Question 6

What is a half-life and why is it useful?

Answer 6

The time taken for the plasma concentration of the drug to halve
- helps the clinician to estimate the frequency of the dosage

Question 7

How do we calculate half life?

Answer 7

• Direct measurement using semi-logarithmic plot of plasma concentration vs time
  or
  t 1/2 = 0.693 / Kel (if we know Kel)

Question 8

What is clearance and how is it calculated?

Answer 8

The volume of plasma cleared of drug per unit time. It most significantly limits the time course of a drug

It can be calculated by Cl = Kel (elimination rate constant) x Vd

Or if we don’t know kel: Cl = (0.693/ t 1/2) x Vd

Question 9

What is the difference between first order and zero order kinetics?

Answer 9

First order is when the plasma drug levels decline at a rate proportional to plasma level. There is an abundance of enzyme, that aren’t saturated. Therefore, the more drug given, the faster it is removed. (curve graph)
Zero order kinetics is when the drug levels decline at a constant linear rate, independent of plasma concentration. (diagonal graph)

Question 10

What is steady state?

Answer 10

The equilibrium point where the amount of drug administered exactly replaces the amount of drug excreted

• Keeps a steady level of drug in the system, in the therapeutic range
• Smaller, frequent doses are better
• it takes 5 half lives to reach a steady state

Question 11

What is a loading dose?

Answer 11

A large first dose, to help get the concentration of drug up to the therapeutic range.
Smaller maintenance doses are then given to keep in this range.

Question 12

What is the equation for Steady state concentration?

Answer 12

Css = (Bioavailability x dose) / (interval of dose x clearance)