Half-time and half-life

[SH4:p7]

Terminology

Elimination half-time vs elimination half-life

T1/2 is important for:

• Duration of action
• Time to steady state (4-5 T1/2)
• Dosing intervals

Elimination half-time

Elimination half-time is time necessary for plasma concentration of a drug to fall to 50% during the elimination phase

• ... is independent of the dose administered
• Does not include the effect of redistribution

NB:

• Looking at propofol [SH4:p156], I believe Stoelting uses elimination half-time as half-life during the beta phase... which could be a slow redistribution phase and is still different from actual elimination halflife quoted by other authors
  --> i.e. Elimination half-time is essentially halflife after the initial rapid redistribution phase, and is not about elimination at all.

Elimination half-life

Elimination half-life is time necessary to eliminate 50% of the drug from the body after an IV bolus

Difference arise between half-time and half-life

Where elimination from body doesn't parallel the plasma concentration
--> elimination half-time and half-life differ

Context-sensitive half-time

Context-sensitive half-time is time necessary for plasma concentration of a drug to fall to 50% after a continuous infusion of a specific duration

• Context refers to the duration
• Context-sensitive half-time generally increases with the duration of infusion
  * Due to less capacity available in inactive tissues for redistribution
• No constant relationship to elimination half-time

Effect-site equilibration time

Effect-site equilibration time is the half-time of equilibration between the drug concentration in plasma and the drug effect
--> Impacts on the time of onset

Examples of short effect-site equilibration time

• Remifentanil
• Alfentanil
• Thiopentone
• Propofol

Examples of longer effect-site equilibration time

• Fentanyl
• Sufentanil
• Midazolam

Decrement times

[From the web] [???] Need more authoritative source

• Decrement time is the time required to decreased the concentration by a certain value after a continuous infusion of a certain duration
  * e.g. context-sensitivie half-time is essentially decrement time for 50% decrease
• Decrement time is plotted on a graph
  * Horizontal axis = duration of infusion
  * Vertical axis = decrement time
• Decrement time may be of more value clinically because it is rare that we wish to reduce the concentration of a drug by precisely 50%