Epidural and Intrathecal

Describe the pharmacokinetics of drugs in the epidural and subarachnoid space

In both spaces, speed of onset is determined by Fick's Law.

Epidural Space

Factors important to epidural administration:

  • Dose given
  • Volume given
    Increased volume increases area of subarachnoid that the drug is in contact with, increasing rate of diffusion.
  • Solubility
    Affected by:
    • pKa and pH
      Determines unionised portion available to cross into CSF.
    • Protein binding
      Determines free drug portion able to cross into CSF.
    • Lipid solubility
  • CSF flow
    Alters concentration gradient between epidural and subarachnoid space.


Factors important to intrathecal administration:

  • Dose
    Much smaller doses required.
  • Volume
    Affects extent of spread.
  • Baricity
    Affects direction of spread:
    • Hyperbaric solutions will sink with gravity
      e.g. Heavy bupivacaine (0.5% bupivacaine with 8% dextrose)
    • Hypobaric solutions will rise against gravity


  1. Peck TE, Hill SA. Pharmacology for Anaesthesia and Intensive Care. 4th Ed. Cambridge University Press. 2014.
  2. ANZCA February/April 2007
  3. Factors influencing distribution of bupivacaine after epidural injection - Diaz Notes.
Last updated 2019-12-14

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