Fentanyl vs Remifentanil (PK/PD)

Master answer

PK and PD of Fentanyl and Remifentanil

Context sensitive half-time

• Defined as the time for plasma concentration to fall to half of its value at the time of stopping an infusion
• A method to describe the variability in plasma concentrations after ceasing an infusion
  The “context” is the duration of infusion.
• Used because terminal elimination half-life has little clinical utility for predicting drug offset
  Half-lives are often misleading when discussing drug infusions.
• Dependent on:
  • Duration of infusion
    During an infusion, drugs distribute out of plasma into tissues. When the infusion ceases, drug is cleared from plasma and tissue drug redistributes back into plasma.
    • The longer an infusion, the more drug has distributed out of tissues, and the longer the redistribution phase
    • The longest context-sensitive half time occurs when an infusion is at steady-state
  • Redistribution
    The maximal CSHT reached depends on the:
    • V_Dss
      Drugs with a larger V_Dss have a longer CSHT, as only a small proportion of the drug in the body will be in plasma and able to be cleared.
    • Rate constant for elimination
      Drugs with a smaller rate constant for elimination have a longer CSHT.

Drugs with longer context-sensitive half-times will wear off less predictably.

Context sensitive half time – Fentanyl vs Remifentanil:

• Fentanyl shows variable CSHT – Has high redistribution, with VdSS 3-5L/kg, and a terminal half life of 3 hours. Hence, prolonged infusion may lead to increased duration of action and SE
• Remifentanil has little redistribution and a small Vd (0.2-0.3L/kg) in the peripheral compartments, and a very short elimination half life of 3 minutes. Hence, it has a very short, context-insensitive half time
  It wears off reliably and quickly following cessation of infusion.

Courtesy: icuprimaryprep.com