Context-sensitive half time


The context-sensitive half-time is the time required for blood or plasma concentrations of a drug to decrease by 50% after discontinuation of drug administration. The context-sensitive half-time often cannot be predicted by the elimination half-life (a measure of the time needed for actual drug metabolism or elimination) because it also depends on drug distribution. It is a useful concept because it helps explain the duration of action of a drug given by infusion after stopping the infusion. It reflects several pharmacokinetic principles:

  • First, as any drug is infused into the body more of the drug will deposit in the body’s tissues (i.e., accumulate) the longer the duration of infusion (or “context” as it is known) until the body’s tissues are completely saturated. Once the drug infusion is stopped this stored drug will then redistribute back into the blood and maintain its effects.
  • Second, every drug accumulates to differing extents, which is largely influenced by the physicochemical properties of the drug.
  • Third, drugs are removed from the blood through two major mechanisms:

    • Distribution: where the drug moves from the blood into the tissues, e.g., fat.
    • Excretion: where the drug is either metabolized (e.g., by the liver) or excreted from the body unchanged (e.g., in urine). Whether or not the metabolites are active is also important.

The context-sensitive half-time is determined by the interaction of all these principles. It is mainly important to know whether a drug has a short, stable context-sensitive half-time, e.g., remifentanil, which will wear off very quickly and predictably after stopping the infusion or a more prolonged, variable context-sensitive half-time, e.g., fentanyl, which will take much longer to wear off and is less predictable.

Similar keyword: Context sensitive 1/2 times


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