Lecture 17: target concentration intervention

Question 1

Target conc

loading dose

MDR

Answer 1

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

Target conc x VOD

Target conc x CL

Question 2

Why does PKPD vary?

Answer 2

1. Systematic (predictable) - 50% (size, disease, genotype)
2. Random (unpredictable) - 50% = between and within subjects

³/₄ allometry explains 67% of CL variaility

³/₄ allometry and maturation explains 80% of CL variability

Question 3

Three ways to dose?

Answer 3

1. Population (same for everyone, often used for adults)
2. Group (covariete guided) - (similar groups, children use)
3. Individual (dose determined form individual response)

Question 4

When should TCI be used?

Answer 4

TCI = Target concentration intervention

1. Usefulness is hard to measure (clinical outcomes are sometimes hard to observe) - (eg. pohenytoin as an anti-convulsant or any anti- drug really)
2. When doing group based dosing and there is big unpredictable variabilty but there is small within subject variability (inadequate beneficial effect or too much adverse effects. Observing response can predict future doses)

Question 5

Target concentration strategy?

Answer 5

1. Choose target conc
2. determine V and CL using weight etc
3. calculate LD and MDR
4. measure response (and revise target conc)
5. measure conc (revise V and CL)
6. Go to step 3 recalculating LD and MDR usign adjusted V and CL

Question 6

Determining group V and CL?

Answer 6

V = V_pop x WT/WTstd

CL = CL_pop x (WT/WT_std)^3/4

Question 7

When do you meaure concentration?

SS estimation?

Answer 7

Normally mesure after a dose or half way between doses, only measure before another dose in the “trough” for drugs like getamicin where you measure multiple times to see the massive range.

SS conc can be approximated to C_tmid

Question 8

TDM and TCI

Answer 8

TDM - Therapeutic drug monitoring

• looks at it as a Therapeutic range and looks to try be within range

TCI - Target concentration intervention

• is more accurate and attempts to work out CL and VOD to readjust doses to get them to the ideal level.