Context-sensitive half-life or context sensitive half-time is defined as the time taken for blood plasma concentration of a drug to decline by one half after an infusion designed to maintain a steady state (i.e. a constant plasma concentration) has been stopped. The "context" is the duration of infusion.
When a drug which has a multicompartmental pharmacokinetic model is given by intravenous infusion it initially will distribute to the central compartment and then move out of this compartment into one or two peripheral compartments. Once this infusion is discontinued, drug continues to move into the peripheral compartments until an equilibrium is reached. At this time, the only way drug may leave plasma is by metabolism or excretion. As the plasma concentration falls, the concentration gradient of drug reverses and drug moves from peripheral compartments back into plasma, maintaining the plasma concentration of the drug, often prolonging the pharmacological effect. If an infusion has reached steady state then the context-sensitive half-life is equal to the terminal plasma half-life of the drug. Otherwise it will be shorter than the terminal elimination half-life.
Remifentanil is relatively context insensitive whilst fentanyl and thiopentone are examples of drugs which have significant context-sensitive changes in their half-life.
The Context-Sensitive Half-Time describes the time required for the plasma drug concentration to decline by 50% after terminating an infusion of a particular duration.
Definition.
It is the time required for drug plasma concentration to decrease by 50% after stopping administration. The drug is administered continuously.
Pharmacokinetics.
Remifentanil is relatively context insensitive. Fentanyl and thiopental are examples of drugs which have significant context-sensitive changes in their half-life.
References.
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