2004B07 Outline the factors that influence the elimination half-life of propofol.



·      Intro

·      Modelling

·      VDSS

·      Clearance



Definition: t1/2β

·  Time taken for plasma propofol concentration to fall by half during terminal elimination phase


·  t1/2β = VDSS/Cl x loge2

Propofol’s numbers

·  Rapid clearance 30-60mL/kg/min

·  But very large volume of distribution 4L/kg

·  Hence long t1/2β 5-12 hours


·  t1/2β rarely affects practice for anaesthetic agents

·  Very slow equilibration with vessel poor group

·  CSHT for propofol is only 50mins at 9 hours’ duration



Compartment diagramme

Washout curve


Volume of distribution at steady state (Vdss)


·  Volume into which the drug appears to disperse


·  High lipid solubility confers

·  Rapid passage into CNS

·  Large VDSS 4L/kg

↓VDSS -> ↓t1/2β

·  ↓Muscle mass (elderly, neonate, cachexia, anorexia)

·  ↓Fat mass (neonate, cachexia, anorexia)

↑VDSS -> ↑t1/2β

·  ↑Muscle mass: athlete

·  ↑Fat mass (propofol lipophilic): obesity




·  Volume of plasma from which drug is removed per unit time


·  Cl 30-60mL/kg/min

·  99.7% metabolized

·  Liver plus ?lung ? kidney ? other (since hepatic blood flow 20mL/kg/min)

·  Phase 1 (3A4, 2B6, 2C19) and 2 (glucuronidation, sulfation)

·  Inactive metabolites

·  High hepatic extraction ratio 0.9


·  ↓Hepatic blood flow (high hepatic extraction ratio hence flow-limited clearance)

o Shock

o LV failure

o Critical illness

o Hypothermia

o Elderly

o Cirrhosis

o ↓Enzymatic activity (must be very severe)

·  Liver failure

o Enzyme inhibition


·  ↑Hepatic blood flow e.g. pregnancy

·  ↑Enzymatic activity e.g. induction (makes minimal difference, extraction ratio 0.9)



Feedback welcome at ketaminenightmares@gmail.com