Context-sensitive half-life or context sensitive half-time is defined as the time taken for

blood plasma Blood plasma is a light amber-colored liquid component of blood in which blood cells are absent, but contains proteins and other constituents of whole blood in suspension. It makes up about 55% of the body's total blood volume. It is the intra ...

concentration of a drug to decline by one half after an infusion designed to maintain a

steady state In systems theory, a system or a Process theory, process is in a steady state if the variables (called state variables) which define the behavior of the system or the process are unchanging in time. In continuous time, this means that for those p ...

(i.e. a constant plasma concentration) has been stopped. The "context" is the duration of infusion. When a drug which has a multicompartmental

pharmacokinetic Pharmacokinetics (from Ancient Greek ''pharmakon'' "drug" and ''kinetikos'' "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to determining the fate of substances administered ...

model is given by

intravenous Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...

infusion Infusion is the process of extracting chemical compounds or flavors from plant material in a solvent such as water, oil or alcohol, by allowing the material to remain suspended in the solvent over time (a process often called steeping). An inf ...

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 (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...

excretion Excretion is a process in which metabolic waste is eliminated from an organism. In vertebrates 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 lea ...

. As the plasma concentration falls, the

concentration gradient Molecular diffusion, often simply called diffusion, is the thermal motion of all (liquid or gas) particles at temperatures above absolute zero. The rate of this movement is a function of temperature, viscosity of the fluid and the size (mass) of ...

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 Terminal may refer to: Computing Hardware * Terminal (electronics), a device for joining electrical circuits together * Terminal (telecommunication), a device communicating over a line * Computer terminal, a set of primary input and output devic ...

of the drug. Otherwise it will be shorter than the terminal elimination half-life.

Remifentanil Remifentanil is a potent, 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 fo ...

is relatively context insensitive whilst

fentanyl Fentanyl, also spelled fentanil, is a very potent synthetic opioid used as a pain medication. Together with other drugs, fentanyl is used for anesthesia. It is also used illicitly as a recreational drug, sometimes mixed with heroin, cocaine ...

and

thiopentone Sodium thiopental, also known as Sodium Pentothal (a trademark of Abbott Laboratories), thiopental, thiopentone, or Trapanal (also a trademark), is a rapid-onset short-acting barbiturate general anesthetic. It is the thiobarbiturate analog of p ...

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.Clinical Anesthesia, 6th Edition. Barash, Cullen, Stoelting, Cahalan, Stock. Lippencott Williams & Wilkins, Philadelphia PA. 2009. Page 818.

Definition

It is the time required for drug plasma concentration to decrease by 50% after stopping administration. The drug is administered continuously.

Pharmacokinetics

* Many drugs follow the multi-compartment model. In other words, a drug may have a preference for a particular body compartment which will result in the majority of that drug to ultimately settle in that particular compartment. ** For highly polar drugs very little will be in the tissues of the body ** For highly lipophilic drugs majority of drug will be located in body tissues * Initially, because the drug is given intravenously, the drug will distribute to the central compartment (i.e. circulation system). The drug (e.g. lipophilic drug) will move out of the central compartment and move into the peripheral compartments ** The movement from one compartment to another is influenced by passive diffusion (Moves from an area of high concentration to one with low concentration) * A drug like fentanyl is very fat soluble. Initial doses ‘wear off’ relatively quickly because the drug redistributes to adipose tissue. However, if the infusion is ongoing then the peripheral compartment (body tissue) will have a large store of fentanyl * The duration of infusion determines whether or not steady state was reached ** Once a drug enters the body, elimination and distribution begins. Initially the drug present in central compartment (i.e. circulation system) is being distributed into the tissues, and being eliminated ** At steady state, the concentration of free drug in the central compartment (i.e. circulation system) is equal to the concentration of free drug in the peripheral compartment (i.e. body tissues) * If steady state is reached, context-sensitive half-life is equal to elimination half-life ** Only free drug that is in the plasma is metabolised ** Metabolism results in the concentration of free drug in the peripheral compartment to decrease ** Due to passive diffusion, free drug will leave the peripheral compartment (i.e. tissues) and enter the central compartment, replenishing any drug that was metabolised from the plasma * If steady state is not reached, context-sensitive half-life is shorter than elimination half-life ** Only free drug that is in the plasma is metabolised ** Overall the entire body has less lipophilic drug. The infusion was stopped earlier. Not as much drug was able to enter the peripheral compartment. ** Because steady state is not reached, the peripheral compartment (i.e. tissues) has less free drug than the central compartment ** The drug continues to move into the peripheral compartment until equilibrium is reached. Remember the drug moves due to passive diffusion. It moves into the peripheral compartment because it has less free drug ** Once equilibrium is reached, the only other way the drug is able to leave the plasma is by elimination. This causes the free drug concentration in the central compartment to fall ** As the plasma concentration falls, the concentration gradient of drug reverses and drug moves from peripheral compartment (i.e. tissues) back into plasma, maintaining the plasma concentration of the drug Remifentanil is relatively context insensitive. Fentanyl and thiopental are examples of drugs which have significant context-sensitive changes in their half-life.

References

{{DEFAULTSORT:Context-Sensitive Half-Life Pharmacokinetics