Pharmacokinetics

Question 1

=How do you recognise if linear/first order PK are present?

Answer 1

Cl, V, F are always constant

AUC and plasma concentrations are proportional to the dose given

Question 2

Why does non-linear PK occur?

Answer 2

As sometimes saturation of enzymes and transporters occur at therapeutic levels

Question 3

What would be the outcome of saturating….

Efflux pumps in the intestinal lumen

Plasma Proteins

Hepatic Enzymes

Answer 3

Efflux Pumps - Drug can more easily enter the cell, as its not being pumped back out, so F increases at higher doses

Plasma Proteins - There will be a higher free fracton of the drug (a) at high concentration, as there are no longer any proteins to bind to!

Hepatic Enzymes - Less of the drug is metabolised, so F increases whilst Cl decreases

Question 4

When the concentration of a drug is much smaller than the Km…what kind of kinetics is being followed?

And what is the effect on clearance?

Answer 4

Linear Kinetics

Clearance is constant due to the first order kinetics…. and so the greater the dose/concentration, the greater the clearance

Question 5

When the concentration is much greater than the Km, what type of kinetics is being followed?

And what is the effect on clearance?

Answer 5

Non-linear kinetics

When this occurs, there is full saturation and so the reaction has reached its Vmax (plateau). Therefore zero order kinetics occurs, with clearance decreasing as concentration increases

Question 6

Why does it take longer to reach the Css of phenytoin as you increase the dose?

Answer 6

As it is non-linear kinetics, so as the dose increases, the clearance decreases

This increases the half life, and so increases the time taken to reach the Css

Question 7

Why are high levels of Vitamin C supplements not needed?

Answer 7

As Vitamin C is reabsorbed actively via saturable transporters….

So once saturation has been reached, no more Vitamin C can be reabsorbed….so clearance decreases