Biological half-life

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.[1] 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.[2]

Biological half-life is an important pharmacokinetic parameter and is usually denoted by the abbreviation .[3]

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.[4][5] 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

SubstanceBiological half-life
Adenosine<10 seconds
Norepinephrine2 minutes
Oxaliplatin14 minutes[6]
Salbutamol1.6 hours
Zaleplon1–2 hours
Morphine2–3 hours
Methotrexate3–10 hours (lower doses), 8–15 hours (higher doses)[7]
Phenytoin12–42 hours
Methadone15 hours to 3 days, in rare cases up to 8 days[8]
Buprenorphine16–72 hours
Clonazepam18–50 hours
Diazepam20–100 hours (active metabolite, nordazepam 1.5–8.3 days)
Flurazepam0.8–4.2 days (active metabolite, desflurazepam 1.75–10.4 days)
Donepezil70 hours (approx.)
Fluoxetine4–6 days (active lipophilic metabolite 4–16 days)
Dutasteride5 weeks
Amiodarone25–110 days
Bedaquiline5.5 months


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.[9]

Peripheral half-life

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.[12] 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.[13][14] 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.[15][16] 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.[12]

Rate equations

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.[17] Thus the fall in plasma concentration after the administration of a single dose is described by the following equation:

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

Half-life is determined by clearance (CL) and volume of distribution (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, 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

Characteristic Description Example value Symbol Formula
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 %

See also


  1. "Half-Life". Medical Subject Headings. United States National Library of Medicine. 2016. Tree No. G01.910.405. Retrieved June 3, 2016.
  2. Lin VW; Cardenas DD (2003). Spinal Cord Medicine. Demos Medical Publishing, LLC. p. 251. ISBN 1-888799-61-7.
  3. IUPAC, Compendium of Chemical Terminology, 2nd ed. (the "Gold Book") (1997). Online corrected version:  (2006) "Biological Half Life".
  4. Nordberg, Gunnar (2007). Handbook on the toxicology of metals. Amsterdam: Elsevier. p. 119. ISBN 0-12-369413-2.
  5. Silk, Kenneth R.; Tyrer, Peter J. (2008). Cambridge textbook of effective treatments in psychiatry. Cambridge, UK: Cambridge University Press. p. 295. ISBN 0-521-84228-X.
  6. Ehrsson, Hans; et al. (Winter 2002). "Pharmacokinetics of oxaliplatin in humans". Medical Oncology. Retrieved 2007-03-28.
  7. Methotrexate - See pharmacology
  8. Manfredonia, John (March 2005). "Prescribing Methadone for Pain Management in End-of-Life Care". JAOA—The Journal of the American Osteopathic Association. 105 (3 supplement): 18S. Retrieved 2007-01-29.
  9. Nikolas C Papanikolaou; Eleftheria G Hatzidaki; Stamatis Belivanis; George N Tzanakakis; Aristidis M Tsatsakis (2005). "Lead toxicity update. A brief review.". Medical Science Monitor. 11 (10): RA329-336.
  10. Griffin et al. 1975 as cited in ATSDR 2005
  11. Rabinowitz et al. 1976 as cited in ATSDR 2005
  12. 1 2 Baribeau, Danielle A; Anagnostou, Evdokia (2015). "Oxytocin and vasopressin: linking pituitary neuropeptides and their receptors to social neurocircuits". Frontiers in Neuroscience. 9. doi:10.3389/fnins.2015.00335. ISSN 1662-453X.
  13. Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 7: Neuropeptides". In Sydor A, Brown RY. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. p. 195. ISBN 9780071481274. Oxytocin can be delivered to humans via nasal spray following which it crosses the blood–brain barrier. ... In a double-blind experiment, oxytocin spray increased trusting behavior compared to a placebo spray in a monetary game with real money at stake.
  14. McGregor IS, Callaghan PD, Hunt GE (May 2008). "From ultrasocial to antisocial: a role for oxytocin in the acute reinforcing effects and long-term adverse consequences of drug use?". British Journal of Pharmacology. 154 (2): 358–68. doi:10.1038/bjp.2008.132. PMC 2442436Freely accessible. PMID 18475254. 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)
  15. Weisman O, Zagoory-Sharon O, Feldman R (2012). "Intranasal oxytocin administration is reflected in human saliva". Psychoneuroendocrinology. 37 (9): 1582–6. doi:10.1016/j.psyneuen.2012.02.014. PMID 22436536.
  16. Huffmeijer R, Alink LR, Tops M, Grewen KM, Light KC, Bakermans-Kranenburg MJ, Ijzendoorn MH (2012). "Salivary levels of oxytocin remain elevated for more than two hours after intranasal oxytocin administration". Neuro Endocrinology Letters. 33 (1): 21–5. PMID 22467107.
  17. Birkett DJ (2002). For example, ethanol may be consumed in sufficient quantity to saturate the metabolic enzymes in the liver, and so is eliminated from the body at an approximately constant rate (zero-order eliminationPharmacokinetics Made Easy (Revised Edition). Sydney: McGraw-Hill Australia. ISBN 0-07-471072-9.
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