15 - Target Conc intervension

Question 1

Target conc equation - loading dose and maintenance dose

Answer 1

Target conc = (target effect x C50) / (emax - effect)

loading dose = V x target conc
maintenance dose = Target conc x clearance

Question 2

Why does PK and PD vary?

Answer 2

predictable - body size, disease state, genotype

Random - between and within subject variability

• however even after accounting for obvious features in groups, there are still differences (in clearance) - eg. weight, sex, age, smoking ect
• Target conc intervention can be used to reduce this variability between people
• however TCI cannot limit the within subject variability

Question 3

3 ways to dose

Answer 3

Everyone same
Group (CLcr, same weight ect. )
Individual - dose determined by individual response - give drug and determine response

Question 4

When to use TCI

Answer 4

• when usefulness is hard to measure - drug is working when the clinical outcome is not easily observable e.g anti-coagulants , use a measure as a substitue to see how the disease state is being treated
• Or when there is a big unpredictable variability and small within subject variablity (this is becase there could be to much variability to get a benefiical effect or get adverse effects) - can observe patient to predict future reposne

Question 5

How to use Target conc stratergy

Answer 5

1. choose target conc
2. degtermine V and CL (group values)
3. Calculate initial LD and MDR using 3.
4. measure response - BP , revise target conc
5. Measure conc , revise V and CL
6. • Back to step 3.

Harder to use PD principles - harder to measure a clinical resposne (effect) that is realted to conc

Question 6

How to determine Group V and CL

Answer 6

V - V = Vpop x Wt/ Wtstd (70kg)
-also body comp

C - CL = CLppop s (wt/wtstd) ^ 3/4
-also use renal function, hepatic fucniton, drugs

Question 7

When to measure conc

• how many times and timing
• example of medicine need to do slightly differnetly

Answer 7

Most medicines only need 1 sample,
Timing - as soon as possible - most mediciens - middle of dosing interval

• then can work out clearance = dose rate / steady state conc (whihc is tmid doses)
• Gentamicin - take 2 sample, and also measure peak and trough -

Question 8

Therapeutic drug monitoring vs Target conc intervention

Answer 8

TDM - measured with a wider range, and can get out of therpautic range however if you are at the very bottom of the range may get no benefiti and if at very top - may get adverse reaction - TDM usually ignore this and say its good as long as ur conc is in this range

TMI - uses PK and PD to identify how patients are different and uses PK guided dose individualizations to get a precise therapeutic target -shown to improve clinical outcome as well as being cost effective