Biological half-life
Overview
The biological half-life or elimination half-life of a substance is the time it takes for a substance (for example a metabolite
Metabolite
Metabolites are the intermediates and products of metabolism. The term metabolite is usually restricted to small molecules. A primary metabolite is directly involved in normal growth, development, and reproduction. Alcohol is an example of a primary metabolite produced in large-scale by industrial...

, drug
Drug
A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...

, signalling molecule, radioactive nuclide
Nuclide
A nuclide is an atomic species characterized by the specific constitution of its nucleus, i.e., by its number of protons Z, its number of neutrons N, and its nuclear energy state....

, or other substance) to lose half of its pharmacologic, physiologic, or radiologic activity, as per the MeSH
Medical Subject Headings
Medical Subject Headings is a comprehensive controlled vocabulary for the purpose of indexing journal articles and books in the life sciences; it can also serve as a thesaurus that facilitates searching...

 definition. In a medical context, half-life may also describe the time it takes for the blood plasma
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 substance to halve ("plasma half-life") its steady-state.
Encyclopedia
The biological half-life or elimination half-life of a substance is the time it takes for a substance (for example a metabolite
Metabolite
Metabolites are the intermediates and products of metabolism. The term metabolite is usually restricted to small molecules. A primary metabolite is directly involved in normal growth, development, and reproduction. Alcohol is an example of a primary metabolite produced in large-scale by industrial...

, drug
Drug
A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...

, signalling molecule, radioactive nuclide
Nuclide
A nuclide is an atomic species characterized by the specific constitution of its nucleus, i.e., by its number of protons Z, its number of neutrons N, and its nuclear energy state....

, or other substance) to lose half of its pharmacologic, physiologic, or radiologic activity, as per the MeSH
Medical Subject Headings
Medical Subject Headings is a comprehensive controlled vocabulary for the purpose of indexing journal articles and books in the life sciences; it can also serve as a thesaurus that facilitates searching...

 definition. In a medical context, half-life may also describe the time it takes for the blood plasma
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 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, active metabolites, and receptor interactions.

Biological half-life is an important pharmacokinetic parameter and is usually denoted by the abbreviation t½.

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, into the environment, follows more complex kinetics
Chemical kinetics
Chemical kinetics, also known as reaction kinetics, is the study of rates of chemical processes. Chemical kinetics includes investigations of how different experimental conditions can influence the speed of a chemical reaction and yield information about the reaction's mechanism and transition...

. See the article rate equation
Rate equation
The rate law or rate equation for a chemical reaction is an equation that links the reaction rate with concentrations or pressures of reactants and constant parameters . To determine the rate equation for a particular system one combines the reaction rate with a mass balance for the system...

.

Water

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
Alcohol
In chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....

 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
Tritiated water
Tritiated water is a form of water where the usual hydrogen atoms are replaced with tritium. In its pure form it may be called tritium oxide or super-heavy water. Pure T2O is corrosive due to self-radiolysis. Diluted, tritiated water is mainly H2O plus some HTO . It is also used as a tracer for...

 (tritium
Tritium
Tritium is a radioactive isotope of hydrogen. The nucleus of tritium contains one proton and two neutrons, whereas the nucleus of protium contains one proton and no neutrons...

). Drinking the same amount of water would have a similar effect, but many would find it difficult to drink a large volume of water. The basis of this decontamination method (used at Harwell
Atomic Energy Research Establishment
The Atomic Energy Research Establishment near Harwell, Oxfordshire, was the main centre for atomic energy research and development in the United Kingdom from the 1940s to the 1990s.-Founding:...

) is to increase the rate at which the water in the body is replaced with new water.

Alcohol

The removal of ethanol
Ethanol
Ethanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a...

 (drinking alcohol
Alcohol
In chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....

) through oxidation by alcohol dehydrogenase
Alcohol dehydrogenase
Alcohol dehydrogenases are a group of dehydrogenase enzymes that occur in many organisms and facilitate the interconversion between alcohols and aldehydes or ketones with the reduction of nicotinamide adenine dinucleotide...

 in the liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...

 from the human body is limited. Hence the removal of a large concentration of alcohol from blood
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....

 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
Methanol
Methanol, also known as methyl alcohol, wood alcohol, wood naphtha or wood spirits, is a chemical with the formula CH3OH . It is the simplest alcohol, and is a light, volatile, colorless, flammable liquid with a distinctive odor very similar to, but slightly sweeter than, ethanol...

 and ethylene glycol
Ethylene glycol
Ethylene glycol is an organic compound widely used as an automotive antifreeze and a precursor to polymers. In its pure form, it is an odorless, colorless, syrupy, sweet-tasting liquid...

. In this way the oxidation of methanol to the toxic formaldehyde
Formaldehyde
Formaldehyde is an organic compound with the formula CH2O. It is the simplest aldehyde, hence its systematic name methanal.Formaldehyde is a colorless gas with a characteristic pungent odor. It is an important precursor to many other chemical compounds, especially for polymers...

 and formic acid
Formic acid
Formic acid is the simplest carboxylic acid. Its chemical formula is HCOOH or HCO2H. It is an important intermediate in chemical synthesis and occurs naturally, most notably in the venom of bee and ant stings. In fact, its name comes from the Latin word for ant, formica, referring to its early...

 in the (human body) can be prevented by giving an appropriate amount of ethanol
Ethanol
Ethanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a...

 to a person who has ingested
Eating
Eating is the ingestion of food to provide for all organisms their nutritional needs, particularly for energy and growth. Animals and other heterotrophs must eat in order to survive: carnivores eat other animals, herbivores eat plants, omnivores consume a mixture of both plant and animal matter,...

 methanol. Note that methanol is very toxic and causes blindness
Blindness
Blindness is the condition of lacking visual perception due to physiological or neurological factors.Various scales have been developed to describe the extent of vision loss and define blindness...

 and death. A person who has ingested ethylene glycol
Ethylene glycol
Ethylene glycol is an organic compound widely used as an automotive antifreeze and a precursor to polymers. In its pure form, it is an odorless, colorless, syrupy, sweet-tasting liquid...

 can be treated in the same way.

Prescription medications

SubstanceHalf-life
Adenosine < 10 seconds
Norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...

2 minutes
Oxaliplatin
Oxaliplatin
Oxaliplatin is a coordination complex that is used in cancer chemotherapy. These platinum-based drugs are usually classified as alkylating agents, although they are not actually alkylating groups ....

14 minutes
Salbutamol
Salbutamol
Salbutamol or albuterol is a short-acting β2-adrenergic receptor agonist used for the relief of bronchospasm in conditions such as asthma and chronic obstructive pulmonary disease. It is marketed as Ventolin among other brand names....

1.6 hours
Morphine
Morphine
Morphine is a potent opiate analgesic medication and is considered to be the prototypical opioid. It was first isolated in 1804 by Friedrich Sertürner, first distributed by same in 1817, and first commercially sold by Merck in 1827, which at the time was a single small chemists' shop. It was more...

2 to 3 hours
Methadone
Methadone
Methadone is a synthetic opioid, used medically as an analgesic and a maintenance anti-addictive for use in patients with opioid dependency. It was developed in Germany in 1937...

15 hours to 3 days, in rare cases up to 8 days.
Fluoxetine
Fluoxetine
Fluoxetine is an antidepressant of the selective serotonin reuptake inhibitor class. It is manufactured and marketed by Eli Lilly and Company...

4 to 6 days*
Dutasteride
Dutasteride
Dutasteride is a dual 5-a reductase inhibitor that inhibits conversion of testosterone to dihydrotestosterone ....

5 weeks
  • The active metabolite
    Metabolite
    Metabolites are the intermediates and products of metabolism. The term metabolite is usually restricted to small molecules. A primary metabolite is directly involved in normal growth, development, and reproduction. Alcohol is an example of a primary metabolite produced in large-scale by industrial...

     of fluoxetine is lipophilic
    Lipophilic
    Lipophilicity, , refers to the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. These non-polar solvents are themselves lipophilic — the axiom that like dissolves like generally holds true...

     and migrates slowly from the brain to the blood. The metabolite has a biological half-life of 4 to 16 days.

Metals

The biological half-life of caesium
Caesium
Caesium or cesium is the chemical element with the symbol Cs and atomic number 55. It is a soft, silvery-gold alkali metal with a melting point of 28 °C , which makes it one of only five elemental metals that are liquid at room temperature...

 in humans is between one and four months. This can be shortened by feeding the person prussian blue
Prussian blue
Prussian blue is a dark blue pigment with the idealized formula Fe718. Another name for the color Prussian blue is Berlin blue or, in painting, Parisian blue. Turnbull's blue is the same substance but is made from different reagents....

. The prussian blue in the digestive system acts as a solid ion exchange
Ion exchange
Ion exchange is an exchange of ions between two electrolytes or between an electrolyte solution and a complex. In most cases the term is used to denote the processes of purification, separation, and decontamination of aqueous and other ion-containing solutions with solid polymeric or mineralic 'ion...

r which absorbs the caesium while releasing potassium
Potassium
Potassium is the chemical element with the symbol K and atomic number 19. Elemental potassium is a soft silvery-white alkali metal that oxidizes rapidly in air and is very reactive with water, generating sufficient heat to ignite the hydrogen emitted in the reaction.Potassium and sodium are...

 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
Physiologically-based pharmacokinetic modelling
-What is a PBPK model?:Physiologically based pharmacokinetic modeling is a mathematical modeling technique for predicting the absorption, distribution, metabolism and excretion of synthetic or natural chemical substances in humans and other animal species...

). 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
EDTA
Ethylenediaminetetraacetic acid, widely abbreviated as EDTA , is a polyamino carboxylic acid and a colourless, water-soluble solid. Its conjugate base is named ethylenediaminetetraacetate. It is widely used to dissolve limescale. Its usefulness arises because of its role as a hexadentate ligand...

 in a chelation therapy
Chelation therapy
Chelation therapy is the administration of chelating agents to remove heavy metals from the body. For the most common forms of heavy metal intoxication—those involving lead, arsenic or mercury—the standard of care in the United States dictates the use of dimercaptosuccinic acid...

, 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
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...

 where it can do the most harm.
  • Polonium
    Polonium
    Polonium is a chemical element with the symbol Po and atomic number 84, discovered in 1898 by Marie Skłodowska-Curie and Pierre Curie. A rare and highly radioactive element, polonium is chemically similar to bismuth and tellurium, and it occurs in uranium ores. Polonium has been studied for...

     in the body has a biological half-life
    Half-life
    Half-life, abbreviated t½, is the period of time it takes for the amount of a substance undergoing decay to decrease by half. The name was originally used to describe a characteristic of unstable atoms , but it may apply to any quantity which follows a set-rate decay.The original term, dating to...

     of about 30 to 50 days.
  • Caesium
    Caesium
    Caesium or cesium is the chemical element with the symbol Cs and atomic number 55. It is a soft, silvery-gold alkali metal with a melting point of 28 °C , which makes it one of only five elemental metals that are liquid at room temperature...

     in the body has a biological half-life of about one to four months.
  • Mercury
    Mercury (element)
    Mercury is a chemical element with the symbol Hg and atomic number 80. It is also known as quicksilver or hydrargyrum...

     (as methylmercury
    Methylmercury
    Methylmercury is an organometallic cation with the formula . It is a bioaccumulative environmental toxicant.-Structure:...

    ) in the body has a half-life of about 65 days.
  • Lead
    Lead
    Lead is a main-group element in the carbon group with the symbol Pb and atomic number 82. Lead is a soft, malleable poor metal. It is also counted as one of the heavy metals. Metallic lead has a bluish-white color after being freshly cut, but it soon tarnishes to a dull grayish color when exposed...

     in bone
    Bone
    Bones are rigid organs that constitute part of the endoskeleton of vertebrates. They support, and protect the various organs of the body, produce red and white blood cells and store minerals. Bone tissue is a type of dense connective tissue...

     has a biological half-life of about ten years.
  • Cadmium
    Cadmium
    Cadmium is a chemical element with the symbol Cd and atomic number 48. This soft, bluish-white metal is chemically similar to the two other stable metals in group 12, zinc and mercury. Similar to zinc, it prefers oxidation state +2 in most of its compounds and similar to mercury it shows a low...

     in bone has a biological half-life of about 30 years.
  • Plutonium
    Plutonium
    Plutonium is a transuranic radioactive chemical element with the chemical symbol Pu and atomic number 94. It is an actinide metal of silvery-gray appearance that tarnishes when exposed to air, forming a dull coating when oxidized. The element normally exhibits six allotropes and four oxidation...

     in bone has a biological half-life of about 100 years.
  • Plutonium
    Plutonium
    Plutonium is a transuranic radioactive chemical element with the chemical symbol Pu and atomic number 94. It is an actinide metal of silvery-gray appearance that tarnishes when exposed to air, forming a dull coating when oxidized. The element normally exhibits six allotropes and four oxidation...

     in the liver has a biological half-life of about 40 years.

First-order elimination

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
    Elimination rate constant
    Elimination rate constant is a value used in pharmacokinetics to calculate the rate at which drugs are removed from the system.It is often abbreviated K or Ke...



The relationship between the elimination rate constant and half-life is given by the following equation:


Half-life is determined by clearance
Clearance (medicine)
In medicine, the clearance is a measurement of the renal excretion ability. Although clearance may also involve other organs than the kidney, it is almost synonymous with renal clearance or renal plasma clearance. Each substance has a specific clearance that depends on its filtration characteristics...

 (CL) and volume of distribution
Volume of distribution
The volume of distribution , also known as apparent volume of distribution, is a pharmacological term used to quantify the distribution of a medication between plasma and the rest of the body after oral or parenteral dosing...

 (VD) and the relationship is described 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
Amiodarone
Amiodarone is an antiarrhythmic agent used for various types of tachyarrhythmias , both ventricular and supraventricular arrhythmias. Discovered in 1961, it was not approved for use in the United States until 1985...

, elimination t½ of about 58 days) are usually started with a loading dose
Loading dose
A loading dose is an initial higher dose of a drug that may be given at the beginning of a course of treatment before dropping down to a lower maintenance dose.A loading dose is most useful for drugs that are eliminated from the body relatively slowly...

 to achieve their desired clinical effect more quickly.

See also

  • Half-life
    Half-life
    Half-life, abbreviated t½, is the period of time it takes for the amount of a substance undergoing decay to decrease by half. The name was originally used to describe a characteristic of unstable atoms , but it may apply to any quantity which follows a set-rate decay.The original term, dating to...

    , pertaining to the general mathematical concept in physics or pharmacology.
  • Effective half-life
    Effective half-life
    Effective half-life denotes the halving of radioactive material in a living organism by means of radioactive decay and biological excretion. A decay constant is needed to calculate the half-life...

The source of this article is wikipedia, the free encyclopedia.  The text of this article is licensed under the GFDL.
 
x
OK