Target Concentration Intervention Flashcards
What two fields of pharmacology does target concentration link?
Pharmacokinetics and pharmacodynamics
What is the equation for target concentration?
Target Conc =
Target effect x C50 / (Emax - target effect)
What does the ideal dose prediction require estimates of?
Emax
C50
V
CL
Of the target concentration what is the equation for the initial peak?
Initial peak = loading dose = Target concentration x Volume of distribution
What is the equation for average steady state with regards to target concentration?
Maintenance dose rate = Target concentration x Clearance
How do we find the target concentration of a drug?
Randomized concentration controlled trials = Gold standard
Why does PKPD vary?
Systemic (predictable)
- Body size
- Disease state (kidney, liver)
- Genotype
Random (not predictable)
- Between subject variability
- Within subject variability
Whats a factor that must be accounted for when finding the clearance of a subject
Age
What is the largest factor to affect clearance?
Individual variability
Clearance = removal or complete inhibition of agent from a system
What are the three methods of dosing?
Population (same for all)
Group (covariate guided, all share same characteristic i.e age)
Individual (dose determined by individual response)
How is renal function determined?
CLCr
Therefore can predict the clearance rate of a patient
What is TCI?
Target Concentration Intervention
How is TCI measured?
The change in disease state caused by a concentration drug as a measure of its effectiveness
What is the problem with using TCI?
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
How is TCI done?
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
Are all drugs cleared at the same rate?
No, depends on half life and the ability of the body to metabolize the drug
How is group V and Cl determined (predictable variability)?
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
Why do we measure blood concentration of drugs?
To determine the CL of an individual
When should blood concentration be measured?
Most medicines - middle of dosing interval (once)
Gentamicin - peak and trough (twice)
Why do most drugs measure concentration mid dosing interval?
AS this will be near the average steady state
Using time of sample, what is the equation for clearance?
Cl = dose rate / concentration at time
Why would be use TCI over therapeutic drug monitoring?
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
Why use TCI?
Single target not a range
Accurate
Why is gentamicin measured twice?
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
