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

·   t1/2 = (VD x loge2) / clearance

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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