Drug Elimination

Question 1

Factors that influence elimination half life:

Answer 1

Effects Vd:
- Aging
- Obesity
- Pathological fluid

Effects CL:
- Cytochrome P450 induction/inhibition decreases/increases t1/2
- Cardiaac/hepatic/renal failure increases t1/2

Question 2

What is clearance (CL) and its equations?

Answer 2

Volume of blood removed (or cleared) of drug per unit of time

CLR = Renal clearance
CLH = Hepatic clearance
CLO = Other clearance routes
CLT = Total clearance

CL is independent of Vd but both determine elimination half life

CL = Rate of drug elimination / (Drug) plasma
Or
CL = Dose/AUC (area under curve)

Question 3

What is elimination half life (t1/2)?

Answer 3

Determines how much time is required for drug to be eliminated from body - extremely useful when designing a therapeutic dosing regimen.

Depends on Vd and CL

t1/2 = (0.693 x Vd) / CL

5 half life’s required to reach steady state

When CL inc t1/2 dec
When CL dec t1/2 inc
When Vd inc t1/2 inc
When Vd dec t1/2 dec

Question 4

Elimination rate equation:

Answer 4

RE = Vmax X (Drug)Plasma / Km + (Drug)Plasma

Vmax = max rate of drug elimination
Km = Drug where rate of elimination is half Vmax
(Drug)Plasma = Drug concentration of plasma