3 - Clearance

Question 1

Clearance Definition and equation

Answer 1

Clearance - Volume of plasma that is cleared of drug per unit time
-describes the relationship between conc and rate of elimination of drug from body

Rate out (mg/h) (or maintenance dose) = CL (L/h) x Conc (mg/L)

Question 2

Things determining clearance

example that is not like this

Answer 2

Main determinant of size of clearance - Blood flow

• cannot have an organ clearance any larger than the blood flow
• Liver - 90mg/hr
• Renal clearance - 70L/hr , also depends on glomerular filtration and tubule secretion

Glygerly trinitrate - very unstable, breaks down by many tissues in boyd, cleraance is not limited to blood flow

Morphine - is metabolized extensively in lover, and its blood clearance approaches liver flow

Theophyline - mainly by liver, but very slow clearnace

Warfarin - even slower - liver metabolsm

Question 3

Clearance classification

Answer 3

Constant - Flow and conc independent (rate of clearance same even if these are different) (although clearance is constant, rate of elimination changes with conc)
First order , linear
e.g - glomerular filtration

Conc dependent - Mixed order

• non-linear, michalis mentin (saturable)
• e.g Renal tubular secretion of penicillin is an active process - that is saturable and thus is mixed order

Flow dependent

• zero order
• usually associated with elimination by liver
• e.g morphine - depends on liver flow (if give with heart failure of slow liver flow then must alter dose as not as much will be cleared)

Question 4

Half life equation

Answer 4

t1/2 = 0.7x V/ CL

Question 5

Clearance classification equation

Answer 5

Rout = vmax/ (Km . C) . C

Vmax - max rate of elimination
Km - 50% of Vmax

• First order (constant) - if drug conc is small compared to Km then conc independentm flow independent - rout = CL. C
• Zero order - if conc large in relation of Km then elimination rate will be independent of conc
• Mixed order -conc that are neither small or large in relation to Km
• general case for all drugs

Question 6

Applications - haemodialysis, haemoperfusion, gut absorption

Answer 6

Haemodialysis - for patients with renal failure, clearance is low, can increase clearance of some other drugs so need to take this into consideration

Haemoperfusion - passing blood through a cartridge designed to absorb drug , can be double this of haemodialysis

Absorption of drug in gut - activated charcol can enjance elimination by preventing primary absorption and reabsirption from drug passing from body back into gut fluids