lecture 17 - target concentration intervention

Question 1

target concentration in clinical use

Answer 1

• target conc. = target effect x C50 / (Emax - target effect)
• LD = TC x V
• MD = TC x CL

used to link PD with PK to predict the right dose for a patient

Question 2

why does PKPD vary?

Answer 2

systematic/predictable
(body size, disease state, genotype, etc.)

random/non-predictable
(between and within subjects)

Question 3

3 ways to dose

Answer 3

• population = same dose for everyone
• group = same dose for similar group (same weight, CLcr, genotype)
• individual = dose determined by individual response (BP, INR, blood conc.)

Question 4

reasons to use target concentration intervention

Answer 4

usefulness hard to measure when drug is working but clinical outcome is not easily observable (eg. anti-arrhythmic drugs)

group based dosing (e.g. using weight) is not enough to reduce the between-subject variability

Question 5

target concentration strategy

Answer 5

1. choose TC
2. determine V and CL
3. calculate LD, MDR
4. measure response; and revise target conc.
5. measure concentration; and revise V and CL
6. back to step 3

Question 6

Determining Group V and CL

Answer 6

volume of distribution

• size
• body composition

clearance

• size
• renal failure
• hepatic function
• concomitant drugs

Question 7

Calculation of LD and MDR

Answer 7

LD = TC x V

MDR = TC x CL

Question 8

when is the least informative time to measure concentrations and when is best

Answer 8

just before the next dose
- the ‘trough’ concentration

CL determines average conc
therefore measuring a conc in the middle of dosing interval will be closer to the average and more useful for predicting CL

Ctmid (conc middle dose interval) = average Css (steady state conc)

Question 9

therapeutic drug monitoring

Answer 9

• drug conc. in therapeutic range
• sub-optimal at borders of the range e.g. top is close to toxic and bottom is close to ineffective
• different to target concentration intervention, where there is a single target (“optimal”)

Question 10

define target concentration interventions

Answer 10

Is a science-based method that uses pharmacokinetic and pharmacodynamic principles to identify how patients are different and uses PK guided dose individualization to achieve a precise therapeutic target.
It has been shown to improve clinical outcome as well as being a cost-effective use of health resources.