2001B09 What do you understand by the term “clearance”?
Using propofol as an example, explain briefly the importance of clearance.

List:

· Intro

· Significance

· Drug comparison

Intro:

Definition	· Volume of plasma from which drug is completely removed per unit time
Units	· mL/kg/min
Equations	· Clearance = VD x k = VD/τ · Total body clearance  = Cl (organ 1) + Cl (organ 2) etc.
Graph	· Clearance = dose/(AUC concentration vs time)

Significance:

Important for	Calculating steady state infusion rate · CSS (mg/mL) = infusion rate (mg/min) / clearance mL/mg/min) Estimating time to offset after long infusion · τ = VD / clearance (where τ  = t1/2 / loge2) Hence determining suitability for long infusion
Irrelevant to	Calculating bolus dose · Dose = Cpt x VDC Estimating time to offset after bolus · Dependent on distribution rate

Drug comparison:

	Propofol	Thiopentone
Site	Liver, ? lung, ? kidney, ? other	Liver
System	Phase: 3A4, 2B6, 2C19	Phase 1: 3A4
Clearance	30-60mL/kg/min (exceeds hepatic blood flow)	3.5mL/kg/min
Enzyme kinetics	First order in physiological range	Zero order in physiological range
t1/2β	5-12 hours	6-15 hours
CSHT	Propofol: short even after long infusion Thiopentone: long even after short infusion

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