The Pharmacokinetics of absorption

Question 1

How does a high hepatic extraction ratio affect bioavailability?

Answer 1

A drug with a high hepatic extraction ratio will be extensively removed during first-pass metabolism (oral dosing) and so will have poor bioavailability.

Question 2

Qorgan x (Fu x Cl int)
Cl organ =   ---------------------------------
                     Qorgan + (Fu x Cl int)
How does this equation change for a low extraction/Cl ratio drug?

Answer 2

Cl organ = Fu x Cl int

Question 3

Qorgan x (Fu x Cl int)
Cl organ =   ---------------------------------
                     Qorgan + (Fu x Cl int)
How does this equation change for a high extraction/Cl ratio drug?

Answer 3

Cl organ = Q organ

Question 4

Would an increase in Fu or Cl intrinsic effect a high ratio clearance drug?

Answer 4

No
Blood flow (Q organ) would be the only factor to effect it

Question 5

How do dosing intervals of oral drug effect Css levels?

Answer 5

A more frequent dosing interval will lead to greater accumulation of drug in the body and so a higher Css value. There will also be less fluctuations in the Css peaks and trophs.

Question 6

Give an example where e-Ka.t is a determinant of the concentration

Answer 6

When the drug is in a modified release formulation and so concentration is controlled

Question 7

How would a lower Ka affect Cmax and Tmax?

Answer 7

if the absorbtion rate is slower it will take longer to reach Cmax and Cmax will also be lower as drug has had more time to be eliminated.

Question 8

How would a higher K affect Cmax and Tmax?

Answer 8

A higher elimination rate would mean that THE Cmax peak would be lower as more drug has been eliminated

Question 9

Why is having large fluctuations between the Cssmax and Cssmin bad?

Answer 9

The Cssmax could be at toxic levels and the Cssmin could be at sub-therapeutic levels.

Question 10

Two drug with different volumes of distribution will have different Cssmax and Cssmin but the Css average will be the same for both. Why?

Answer 10

Because the clearance and dose rate haven’t changed. Volume of distribution doesn’t affect Css average.

Question 11

What is AUC?

Answer 11

The area under the curve for a concentration-time graph starting from time zero to time infinity.
Its a measure of the body’s exposure to a drug reflecting both input and elimination