PK 2

Question 1

What is meant by quantitative pahrmokinetics?

Answer 1

Changes in plasma/ tissue drug concentration with time

Question 2

What is the drug absorption rate?

Answer 2

The amount of drug absorbed from administration site to measurement site per unit time

Question 3

What order of kinetics does oral/ IM routes take?

Answer 3

First order
(zero order= IV infusion)

Question 4

What are the kinetics from IV bolus administration?

Answer 4

Considered instant

Question 5

Describe first order kinetics

Answer 5

• Absorption rate is proportional to amount of drug

Question 6

Describe 0 order kinetics

Answer 6

-Absorption rate increases in a linear fashion with time. INDEPENDENT of amount of drug delivered.

Question 7

What is the drug elimination rate?

Answer 7

Amount of PARENT drug eliminated from the body PER UNIT TIME

with respect to IRREVERSIBLE elimination of parent drug

Question 8

What is Vi?

Answer 8

Initial volume - blood + interstitial fluid

Question 9

Define Vd

Answer 9

Volume into which a drug appears to be distributed with a concentration equal to that of plasma
- Amount of drug in body at time (t)= Vd at time x blood/plasma conc at time

Question 10

What affects Vd?

Answer 10

The affinity of the drug for plasma and tissue. Some prefer to move to tissues and so have a higher Vd

Question 11

If Vd is 0.1-0.3L/kg what does it tell you about the drug?

Answer 11

That is is most likely water soluble and moves mainly to the ECF

Question 12

If Vd is 0.6l/kg what does it tell you about the drug?

Answer 12

that most likely it distributes to BOTH ECF and ICF

Question 13

If Vd is around 2l/kg what does it tell you about the drug?

Answer 13

that most likely is it accumulating at a particular site e.g. fat

Question 14

What is total body (blood) clearance

Answer 14

The volume of blood/ plasma cleared of parent drug per unit time
(imagine it as flow rate)

Question 15

How do you calculate elimination and clearance?

Answer 15

• Rate of elim= blood clearance x blood concentration

- Total clearance = Cl hep + Cl ren + Cl pulmonary

Question 16

How do you determine total CL after IV bolus?

Answer 16

-Plasma clearance after IV bolus= Dose/ AUC

Question 17

Describe bioavailability and calculating CL

Answer 17

Bio= the EXTENT (amount) of absorption from admin site to measurement site
F= (Dose iv/ Dose oral)  X (AUC oral/ AUC iv)

Question 18

How do you calculate the elimination rate constant K?

Answer 18

=Clearance/ Vd

Question 19

What is the elimination rate constant?

Answer 19

Constant relating to rate of elimination to the amount of drug in the body

Question 20

How do you calculate the rate of elimination?

Answer 20

Plasma Cl x plasma concentration

Question 21

Describe the one compartment model

Answer 21

• Assumed drug is instantly distributed
• Cl, Cd and half life are CONSTANT (exponential)
• therefore decay= Vd= Vi= Dose (C0)

Question 22

What does the half life equal in a single compartment model?

Answer 22

natural log of 2 / elim K

0.0693 x Vd /Cl

Question 23

In the 2 compartment model why is there 2 half lives and which is generally more important?

Answer 23

• Because of a change in Vd (implies Vs initially increases)

- Normally B but not always (the one with the biggest AUC)

Question 24

How does Vd relate to kinetics of drug elimination?

Answer 24

• Phase 1: drug partitions into tissues

- Phase 2: drug slowly cleared from tissues

Question 25

On average how many half lives does it take to reach steady state in multiple dosing?

Answer 25

around 5

Question 26

How do you calculate average concentration ss?

Answer 26

Avrgconc ss = (Therapeutic dose x F)/ (CL x dosing interval)

Question 27

Is Average concentration ss dependant upon Vd?

Answer 27

No it is independant

Question 28

What is a loading dose?

Answer 28

An initial higher dose that it given to load up the tissues so you reach steady state quicker. You then drop down to maintenance dose.
Most useful for drugs that are eliminated slowly (have a long half life)
-Loading dose= (Therapeutic Css X Vss) / F

Question 29

What is the importance of plasma half life and dosing frequency?

Answer 29

• Peak to trough is large when only giving 1 dose a day, means you run the risk of falling out the therapeutic window. Dosing more frequently can stop this.

Question 30

Is plasma clearance always linear?

Answer 30

No

• it is driven by enzyme/ transported kinetics so saturation can occur.
• Vm x C/ Km x C