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Flashcards in PK 3 Deck (20)
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1

What is the benefit of PBPK?

Very useful for predicting PK across species

2

Using PBPK how can Vd be predicted?

By a knowledge of drug plasma protein and tissue binding

3

Using PBPK how can CL be predicted?

Using allometry or in vitro enzymes kinetics

4

What is Kleibers law?

Mass specific metabolic rate needed to sustain an organism decreases with body weight to the 1/4 power
i.e. Mass specific metabolic rate = constant x BW^0.25

5

What impact does allometry have on clearance?

-The smaller the animal the greater the drug clearance
- Larger an animal is the lower the blood flow and as plasma clearance is dependent on blood flow clearance is also less in larger animals.
-BUT application of this theory less reliable on drug metabolism clearance due to enzymes- different species have different enzymes

6

What is intrinsic clearance?

The enzyme mediated clearance that would occur without physiological limitations

7

How do you calculate CLintrinsic?

Vmax/ Km

8

What limits the clearance of high clearance drugs?

Blood flow

9

How do you calculate the clearance for low clearance drugs?

fraction unbound x intrinsic clearance of the liver

10

What are the reasons for variation in PPB?

- Elderly/ neonates have less proteins
- Disease states can affeect concentration
- Drugs may be displaced from plasma proteins by other drugs that have a higher affinity

11

What will happen to CL and Vd if PPB increases?

They will decrease

12

What is free drug concentration?

It is the effective concentration->it drives the effects. So if PPB decreased causing an increase in CL and Vd then free drug conc would stay the same.

13

From a clinical point of view is a change in PPB an issue?

Normally no
3 exceptions:
- Rapid IV bolus
- Parenteral administration of displaced drug with high organ extraction ratio
- Therapeutic drug monitoring and drug displacement from plasma binding site

14

What is the problem with rapid IV bolus?

-The rapid admin of the displacement agent could cause free conc to increase due to rapid displacement of displaced drug before redistribution occured.
-It will equilibriate and then not an issue
-e.g. sulfamide + bilirubin= Kernicterus

15

Explain therapeutic drug monitoring and drug binding displacement from plasma binding

- e.g.
Phenytoin alone(Ctotal=20)
Phenytoin + Valproic acid (Ctotal= 15)
- No dosage adjustment needed though because although Ctot decreases, fu Increases so C free doesn't change

16

Describe the advantages controlled release drug therapy

- Advantages:
Similar kinetics to IV infusion (0 order)
Reduced risk of breaching therapeutic window
Drug delivery period can be over several months from 1 administration

17

What is the depot effect?

- Drug diffusion/ release= K x (drug conc at depot surface)
-K = the drug release constant
-Works like a bar of soap, outside film dissolves at a constant rate so specific amount of drug administered and the rest is sequestered inside.

18

What is the Paratect bolus morantel system>

-Delivers morantel tartare for up to 90 days
- Controled release occurs through discs at the ends and the rest is sequestered inside.

19

How do spot on anthelmintics work as controlled release drugs?

-They are oil based as so the drug is sequestered inside sebaceous glands and released with sebum at a constant rate

20

How does the osmotic ruminal therapeutic system work?

Contact with water swells capsule via osmosis which pushes flow moderator releasing controlled, constant amount of drug