Target Concentration Intervention

Question 1

What two fields of pharmacology does target concentration link?

Answer 1

Pharmacokinetics and pharmacodynamics

Question 2

What is the equation for target concentration?

Answer 2

Target Conc =

Target effect x C50 / (Emax - target effect)

Question 3

What does the ideal dose prediction require estimates of?

Answer 3

Emax
C50
V
CL

Question 4

Of the target concentration what is the equation for the initial peak?

Answer 4

Initial peak = loading dose = Target concentration x Volume of distribution

Question 5

What is the equation for average steady state with regards to target concentration?

Answer 5

Maintenance dose rate = Target concentration x Clearance

Question 6

How do we find the target concentration of a drug?

Answer 6

Randomized concentration controlled trials = Gold standard

Question 7

Why does PKPD vary?

Answer 7

Systemic (predictable)

• Body size
• Disease state (kidney, liver)
• Genotype

Random (not predictable)

• Between subject variability
• Within subject variability

Question 8

Whats a factor that must be accounted for when finding the clearance of a subject

Answer 8

Age

Question 9

What is the largest factor to affect clearance?

Answer 9

Individual variability

Clearance = removal or complete inhibition of agent from a system

Question 10

What are the three methods of dosing?

Answer 10

Population (same for all)
Group (covariate guided, all share same characteristic i.e age)
Individual (dose determined by individual response)

Question 11

How is renal function determined?

Answer 11

CLCr

Therefore can predict the clearance rate of a patient

Question 12

What is TCI?

Answer 12

Target Concentration Intervention

Question 13

How is TCI measured?

Answer 13

The change in disease state caused by a concentration drug as a measure of its effectiveness

Question 14

What is the problem with using TCI?

Answer 14

1) usefulness is hard to measure in instances when clinical outcomes are not easily observed
i.e anti-arrhythmias (dont occur all the time)
anti-convulsants (dont happen all the time)

2) Unpredictable variability between patients
3) requires small within subject variability

Question 15

How is TCI done?

Answer 15

1) Choose target concentration
2) Determine V and CL
3) Calculate LD and MDR
4) Measure response and revise TC
5) Measure concentration (revise V and CL if need be)
6) Go back to step 3 (basically repeat until desired response is achieved)

Best method for determining individual dose

Question 16

Are all drugs cleared at the same rate?

Answer 16

No, depends on half life and the ability of the body to metabolize the drug

Question 17

How is group V and Cl determined (predictable variability)?

Answer 17

Volume of distribution:
Size, v = Vpop x WT (patient weight)/ WTstd
- factor is body composition

Clearance
size Cl = Clpop x (WT/WTstd)3/4 (allometric observation theory)

Factors

• renal function
• Hepatic function
• concomitant drugs

Question 18

Why do we measure blood concentration of drugs?

Answer 18

To determine the CL of an individual

Question 19

When should blood concentration be measured?

Answer 19

Most medicines - middle of dosing interval (once)

Gentamicin - peak and trough (twice)

Question 20

Why do most drugs measure concentration mid dosing interval?

Answer 20

AS this will be near the average steady state

Question 21

Using time of sample, what is the equation for clearance?

Answer 21

Cl = dose rate / concentration at time

Question 22

Why would be use TCI over therapeutic drug monitoring?

Answer 22

TDM is bad because if the drug is in the range then no more is given even if its at the bottom of the range and having no effect, therefore it is IMPRECISE

Question 23

Why use TCI?

Answer 23

Single target not a range

Accurate

Question 24

Why is gentamicin measured twice?

Answer 24

It has a half life, therefore it has a peak and a trough of activity in the body. Measuring twice tells you the half life and this can be used to calculate the clearance

Cl = V x K

T0.5 = ln (2) / K