Context-sensitive half-life
Encyclopedia
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 elimination 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.
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
concentration of a drug to decline by one half after an infusion designed to maintain a steady state
Steady state
A system in a steady state has numerous properties that are unchanging in time. This implies that for any property p of the system, the partial derivative with respect to time is zero:...
(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
Infusion
An infusion is the outcome of steeping plants with desired chemical compounds or flavors in water or oil.-History:The first recorded use of essential oils was in the 10th or 11th century by the Persian polymath Avicenna, possibly in The Canon of Medicine.-Preparation techniques:An infusion is very...
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
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
or excretion
Excretion
Excretion is the process by which waste products of metabolism and other non-useful materials are eliminated from an organism. This is primarily carried out by the lungs, kidneys and skin. This is in contrast with secretion, where the substance may have specific tasks after leaving the cell...
. 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 elimination half-life of the drug. Otherwise it will be shorter than the terminal elimination half-life.
Remifentanil
Remifentanil
Remifentanil is a potent ultra short-acting synthetic opioid analgesic drug. It is given to patients during surgery to relieve pain and as an adjunct to an anaesthetic. Remifentanil is used for sedation as well as combined with other medications for use in general anesthesia...
is relatively context insensitive whilst fentanyl and thiopentone are examples of drugs which have significant context-sensitive changes in their half-life.