The biological half-life or terminal half-life of a substance is the time it takes for a substance (for example a metabolite, drug, signalling molecule, radioactive nuclide, or other substance) to lose half of its pharmacologic, physiologic, or radiologic activity, according to the Medical Subject Headings (MeSH) definition. Typically, this refers to the body's cleansing through the function of kidneys and liver in addition to excretion functions to eliminate a substance from the body. In a medical context, half-life may also describe the time it takes for the blood plasma concentration of a substance to halve (plasma half-life) its steady-state. The relationship between the biological and plasma half-lives of a substance can be complex depending on the substance in question, due to factors including accumulation in tissues (protein binding), active metabolites, and receptor interactions.
While a radioactive isotope decays perfectly according to first order kinetics where the rate constant is fixed, the elimination of a substance from a living organism follows more complex chemical kinetics. See Rate equation.
The biological half-life of water in a human is about 7 to 14 days. It can be altered by behavior. Drinking large amounts of alcohol will reduce the biological half-life of water in the body. This has been used to decontaminate humans who are internally contaminated with tritiated water (tritium). The basis of this decontamination method (used at Harwell) is to increase the rate at which the water in the body is replaced with new water.
The removal of ethanol (drinking alcohol) through oxidation by alcohol dehydrogenase in the liver from the human body is limited. Hence the removal of a large concentration of alcohol from blood may follow zero-order kinetics. Also the rate-limiting steps for one substance may be in common with other substances. For instance, the blood alcohol concentration can be used to modify the biochemistry of methanol and ethylene glycol. In this way the oxidation of methanol to the toxic formaldehyde and formic acid in the human body can be prevented by giving an appropriate amount of ethanol to a person who has ingested methanol. Note that methanol is very toxic and causes blindness and death. A person who has ingested ethylene glycol can be treated in the same way. Half life is also relative to the subjective metabolic rate of the individual in question.
Common prescription medications
|Methadone||15 hours to 3 days, in rare cases up to 8 days|
|Diazepam||20–100 hours (active metabolite, nordazepam 1.5–8.3 days)|
|Flurazepam||0.8–4.2 days (active metabolite, desflurazepam 1.75–10.4 days)|
|Donepezil||70 hours (approx.)|
|Fluoxetine||4–6 days (active lipophilic metabolite 4–16 days)|
The biological half-life of caesium in humans is between one and four months. This can be shortened by feeding the person prussian blue. The prussian blue in the digestive system acts as a solid ion exchanger which absorbs the caesium while releasing potassium ions.
For some substances, it is important to think of the human or animal body as being made up of several parts, each with their own affinity for the substance, and each part with a different biological half-life (physiologically-based pharmacokinetic modelling). Attempts to remove a substance from the whole organism may have the effect of increasing the burden present in one part of the organism. For instance, if a person who is contaminated with lead is given EDTA in a chelation therapy, then while the rate at which lead is lost from the body will be increased, the lead within the body tends to relocate into the brain where it can do the most harm.
- Polonium in the body has a biological half-life of about 30 to 50 days.
- Caesium in the body has a biological half-life of about one to four months.
- Mercury (as methylmercury) in the body has a half-life of about 65 days.
- Lead in the blood has a half life of 28–36 days.
- Lead in bone has a biological half-life of about ten years.
- Cadmium in bone has a biological half-life of about 30 years.
- Plutonium in bone has a biological half-life of about 100 years.
- Plutonium in the liver has a biological half-life of about 40 years.
Some substances may have different half-lives in different parts of the body. For example, oxytocin has a half-life of typically about three minutes in the blood when given intravenously. Peripherally administered (e.g. intravenous) peptides like oxytocin cross the blood-brain-barrier very poorly, although very small amounts (< 1%) do appear to enter the central nervous system in humans when given via this route. In contrast to peripheral administration, when administered intranasally via a nasal spray, oxytocin reliably crosses the blood–brain barrier and exhibits psychoactive effects in humans. In addition, also unlike the case of peripheral administration, intranasal oxytocin has a central duration of at least 2.25 hours and as long as 4 hours. In likely relation to this fact, endogenous oxytocin concentrations in the brain have been found to be as much as 1000-fold higher than peripheral levels.
There are circumstances where the half-life varies with the concentration of the drug. Thus the half-life, under these circumstances, is proportional to the initial concentration of the drug A0 and inversely proportional to the zero-order rate constant k0 where:
This process is usually a logarithmic process - that is, a constant proportion of the agent is eliminated per unit time. Thus the fall in plasma concentration after the administration of a single dose is described by the following equation:
- Ct is concentration after time t
- C0 is the initial concentration (t=0)
- k is the elimination rate constant
The relationship between the elimination rate constant and half-life is given by the following equation:
In clinical practice, this means that it takes 4 to 5 times the half-life for a drug's serum concentration to reach steady state after regular dosing is started, stopped, or the dose changed. So, for example, digoxin has a half-life (or t½) of 24–36 h; this means that a change in the dose will take the best part of a week to take full effect. For this reason, drugs with a long half-life (e.g., amiodarone, elimination t½ of about 58 days) are usually started with a loading dose to achieve their desired clinical effect more quickly.
Sample values and equations
|Dose||Amount of drug administered.||500 mg||Design parameter|
|Dosing interval||Time between drug dose administrations.||24 h||Design parameter|
|Cmax||The peak plasma concentration of a drug after administration.||60.9 mg/L||Direct measurement|
|tmax||Time to reach Cmax.||3.9 h||Direct measurement|
|Cmin||The lowest (trough) concentration that a drug reaches before the next dose is administered.||27.7 mg/L||Direct measurement|
|Volume of distribution||The apparent volume in which a drug is distributed (i.e., the parameter relating drug concentration to drug amount in the body).||6.0 L|
|Concentration||Amount of drug in a given volume of plasma.||83.3 mg/L|
|Elimination half-life||The time required for the concentration of the drug to reach half of its original value.||12 h|
|Elimination rate constant||The rate at which a drug is removed from the body.||0.0578 h−1|
|Infusion rate||Rate of infusion required to balance elimination.||50 mg/h|
|Area under the curve||The integral of the concentration-time curve (after a single dose or in steady state).||1,320 mg/L·h|
|Clearance||The volume of plasma cleared of the drug per unit time.||0.38 L/h|
|Bioavailability||The systemically available fraction of a drug.||0.8|
|Fluctuation||Peak trough fluctuation within one dosing interval at steady state||41.8 %||
- Half-life, pertaining to the general mathematical concept in physics or pharmacology.
- Effective half-life
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Recent studies also highlight remarkable anxiolytic and prosocial effects of intranasally administered OT in humans, including increased ‘trust’, decreased amygdala activation towards fear-inducing stimuli, improved recognition of social cues and increased gaze directed towards the eye regions of others (Kirsch et al., 2005; Kosfeld et al., 2005; Domes et al., 2006; Guastella et al., 2008)
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