L4: Pharmacokinetics I

Question 1

A bit about interspecies variability.

Answer 1

Effective drug plasma concentrations are often preserved across the species.

Drug metabolism exhibits interspecies variation: dose rates differ from species to species.

Question 2

What is the Dose-Response Curve?

Answer 2

• Gives us the effective range of concentrations for a drug.

Question 3

What is EC90?

Answer 3

The 90% effective concentration which becomes the target concentration to be obtained in blood during clinical trials.

Question 4

What is the concentration versus time curve? (C-T)

Answer 4

Depicts the combined processes of distribution, metabolism and elimination.

Volume of distribution, clearance and half life can then be calculated.

Gives us the neccesary PK parameters to calculate a dose rate for further studies.

Question 5

What is the clearance?

Answer 5

• Most important PK parameter
• Determines the dose rate required to maintain a plasma concentration
• Helps us determine how much drug needs to be administered each time, usually expressed in mg/kg

Question 6

How do you calculate the Clearance?

Answer 6

Cl = Dose/AUC

Question 7

What does Cpss stand for and what are some calculations associated with this?

Answer 7

Cpss = steady state plasma drug concentration.

At Cpss rate of admin = rate of elimination

Rate of elimination = Cl x Cp

Rate of admin = Cl x Cpss

Maintanence dose rate = Cl x Cpss

Question 8

How is maintanence dose rate expressed?

Answer 8

mg/kg/unit time

Question 9

How do you calculate loading dose?

Answer 9

LD = Vd x target C

Where:

Vd = vol. of distrib

target C = IV conc. desired based on d-r curves

Question 10

What can be achieved with a loading dose?

Answer 10

Steady state concentrations (Cpss)

Question 11

What does C0 stand for and what is it used for?

Answer 11

Concentration time at zero.

Used to calculate PK parameter Vd

Often practically difficult to obtain because of time required for drug to move around the body in the circulation.

C0 often estimated by extrapolation from data points within the distribution phase?

Question 12

What is the elimination half life?

Answer 12

The time for the concentration of the drug in plasma (or the amount of drug in the body) to halve. It determines the dose interval.

Question 13

Elimination is proportional to what?

Answer 13

Plasma concentration

Question 14

What is bioavailability?

Answer 14

The rate and extent of absorption.

Question 15

What is pharmacokinetics?

Answer 15

Study of the time course of drug absorption, distribution, metabolism and excretion.

What the body does to the drug.

Question 16

What is pharmadynamics?

Answer 16

What a drug does to the body.

Question 17

Are dose response curves usually performed in vitro?

Answer 17

yes

Question 18

< AUC = ? Cl

> AUC = ?Cl

Answer 18

• < AUC = > Cl
• > AUC = < Cl

Question 19

How many half lives are required to reach Css?

Answer 19

4 - 5

Question 20

A smaller AUC means the drug is distributed faster or slower?

Answer 20

faster

Question 21

Draw a diagram showing where the eliminatio phase is on a CT curve

Answer 21

Question 22

What is 1st order elimination?

What is zero order elimination?

Answer 22

• 1st order elim:
• exponential decay
• a constant fraction of the drug is eliminated per unit time
• zero order elim:
• a set amount of drug is metabolised per unit time