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Biological half-life

(Redirected fromElimination half life)

Biological half-life(elimination half-life,pharmacological half-life) is the time taken for concentration of abiological substance(such as amedication) to decrease from its maximumconcentration(Cmax) to half of Cmaxin theblood plasma.[1][2][3][4][5]It is denoted by the abbreviation.[2][4]

Graph of drug plasma concentrations over 96 hours
Time course of drug plasma concentrations over 96 hours following oral administrations every 24 hours (τ). Absorption half-life 1 h, elimination half-life 12 h.

This is used to measure the removal of things such asmetabolites,drugs,andsignalling moleculesfrom the body. Typically, the biological half-life refers to the body's naturaldetoxification(cleansing) throughliver metabolismand through theexcretionof the measured substance through the kidneys and intestines. This concept is used when the rate of removal is roughlyexponential.[6]

In a medical context, half-life explicitly describes the time it takes for theblood plasmaconcentration of a substance to halve (plasma half-life) its steady-state when circulating in the full blood of anorganism.This measurement is useful in medicine,pharmacologyandpharmacokineticsbecause it helps determine how much of a drug needs to be taken and how frequently it needs to be taken if a certain average amount is needed constantly. By contrast, the stability of a substance in plasma is described asplasma stability.This is essential to ensure accurate analysis of drugs in plasma and fordrug discovery.

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.[7]

Examples

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Water

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The biological half-life of water in a human is about 7 to 14 days. It can be altered by behavior. Drinking large amounts ofalcoholwill reduce the biological half-life of water in the body.[8][9]This has been used to decontaminate patients who are internally contaminated withtritiated water.The basis of this decontamination method is to increase the rate at which the water in the body is replaced with new water.

Alcohol

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The removal ofethanol(drinking alcohol) through oxidation byalcohol dehydrogenasein theliverfrom the human body is limited. Hence the removal of a large concentration of alcohol frombloodmay followzero-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 ofmethanolandethylene glycol.In this way the oxidation of methanol to thetoxicformaldehydeandformic acidin the human body can be prevented by giving an appropriate amount ofethanolto a person who hasingestedmethanol. Methanol is very toxic and causesblindnessand death. A person who has ingestedethylene glycolcan be treated in the same way. Half life is also relative to the subjective metabolic rate of the individual in question.

Common prescription medications

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Substance Biological half-life
Adenosine Less than 10 seconds (estimate)[10]
Norepinephrine 2 minutes[11]
Oxaliplatin 14 minutes[12]
Zaleplon 1 hour[13]
Morphine 1.5–4.5 hours[14]
Flurazepam 2.3 hours[15]

Active metabolite (N-desalkylflurazepam): 47–100 hours[15]

Methotrexate 3–10 hours (lower doses),

8–15 hours (higher doses)[16]

Methadone 15–72 hours

in rare cases up to 8 days[17]

Diazepam 20–50 hours[18]

Active metabolite (nordazepam): 30–200 hours[18]

Phenytoin 20–60 hours[19]
Buprenorphine 28–35 hours[20]
Clonazepam 30–40 hours[21]
Donepezil 3 days (70 hours)[22]
Fluoxetine 4–6 days (under continuous administration)[23]

Active lipophilic metabolite (norfluoxetine): 4–16 days[23]

Amiodarone 14–107 days[24]
Vandetanib 19 days[25]
Dutasteride 21–35 days (under continuous administration)[26]
Bedaquiline 165 days[27]

Metals

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The biological half-life ofcaesiumin humans is between one and four months. This can be shortened by feeding the personprussian blue.The prussian blue in the digestive system acts as a solidion exchangerwhich absorbs the caesium while releasingpotassiumions.

For some substances, it is important to think of the human or animal body as being made up of several parts, each with its 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 givenEDTAin achelation 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 thebrainwhere it can do the most harm.[28]

  • Poloniumin the body has a biologicalhalf-lifeof about 30 to 50 days.
  • Caesiumin the body has a biological half-life of about one to four months.
  • Mercury(asmethylmercury) in the body has a half-life of about 65 days.
  • Lead in the blood has a half life of 28–36 days.[29][30]
  • Leadinbonehas a biological half-life of about ten years.
  • Cadmiumin bone has a biological half-life of about 30 years.
  • Plutoniumin bone has a biological half-life of about 100 years.
  • Plutoniumin the liver has a biological half-life of about 40 years.

Peripheral half-life

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Some substances may have different half-lives in different parts of the body. For example,oxytocinhas ahalf-lifeof typically about three minutes in the blood when givenintravenously.Peripherally administered (e.g. intravenous) peptides like oxytocin cross theblood-brain-barriervery poorly, although very small amounts (< 1%) do appear to enter thecentral nervous systemin humans when given via this route.[31]In contrast to peripheral administration, when administeredintranasallyvia a nasal spray, oxytocin reliably crosses theblood–brain barrierand exhibitspsychoactiveeffects in humans.[32][33]In addition, unlike the case of peripheral administration, intranasal oxytocin has a central duration of at least 2.25 hours and as long as 4 hours.[34][35]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.[31]

Rate equations

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Main article:Rate equation
See also:Pharmacokinetics § Metrics

First-order elimination

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Timeline of an exponential decay process[36][37][38]
Time (t) Percent of initial value Percent completion
t⁠1/2⁠ 50% 50%
t⁠1/2⁠× 2 25% 75%
t⁠1/2⁠× 3 12.5% 87.5%
t⁠1/2⁠× 3.322 10.00% 90.00%
t⁠1/2⁠× 4 6.25% 93.75%
t⁠1/2⁠× 4.322 5.00% 95.00%
t⁠1/2⁠× 5 3.125% 96.875%
t⁠1/2⁠× 6 1.5625% 98.4375%
t⁠1/2⁠× 7 0.78125% 99.21875%
t⁠1/2⁠× 10 ~0.09766% ~99.90234%

Half-times apply to processes where the elimination rate is exponential. Ifis the concentration of a substance at time,its time dependence is given by

wherekis thereaction rate constant.Such a decay rate arises from afirst-order reactionwhere the rate of elimination is proportional to the amount of the substance:[39]

The half-life for this process is[39]

Alternatively, half-life is given by

whereλzis the slope of the terminal phase of the time–concentration curve for the substance on a semilogarithmic scale.[40][41]

Half-life is determined byclearance(CL) andvolume 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 t⁠1/2⁠) 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 t⁠1/2⁠of about 58 days) are usually started with aloading doseto achieve their desired clinical effect more quickly.

Biphasic half-life

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Many drugs follow a biphasic elimination curve — first a steep slope then a shallow slope:

STEEP (initial) part of curve —> initial distribution of the drug in the body.
SHALLOW part of curve —> ultimate excretion of drug, which is dependent on the release of the drug from tissue compartments into the blood.

The longer half-life is called theterminal half-lifeand the half-life of the largest component is called thedominant half-life.[39]For a more detailed description seePharmacokinetics § Multi-compartmental models.

See also

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References

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  1. ^"Elimination Half-Life".Pharmacology in one semester.Archived fromthe originalon 22 October 2020.Retrieved20 February2020.
  2. ^ab"Definition of Half-Life (t1⁄2) ".AIDSinfo.19 February 2020. Archived fromthe originalon 20 February 2020.Retrieved20 February2020.
  3. ^Curry, Stephen H. (1993). "PHARMACOKINETICS OF ANTIPSYCHOTIC DRUGS".Antipsychotic Drugs and their Side-Effects.Elsevier. pp. 127–144.doi:10.1016/b978-0-12-079035-7.50015-4.ISBN978-0-12-079035-7.The elimination half-life measures the kinetics of loss of drug from the body as a whole once all distribution equilibria have been achieved.
  4. ^abDasgupta, Amitava; Krasowski, Matthew D. (2020). "Pharmacokinetics and therapeutic drug monitoring".Therapeutic Drug Monitoring Data.Elsevier. pp. 1–17.doi:10.1016/b978-0-12-815849-4.00001-3.ISBN978-0-12-815849-4.S2CID209258489.The half-life of a drug is the time required for the serum concentration to be reduced by 50%. Once the half-life of the drug is known, the time required for clearance can be estimated. Approximately 97% of the drug is eliminated by 5 halflives, while ~99% is eliminated by 7 half-lives.
  5. ^Toutain, P. L.; Bousquet-Melou, A. (2004)."Plasma terminal half-life"(PDF).Journal of Veterinary Pharmacology and Therapeutics.27(6): 427–439.doi:10.1111/j.1365-2885.2004.00600.x.PMID15601438.Archived fromthe original(PDF)on 20 February 2020.Following i.v. administration, the terminal half-life is the time required for plasma/blood concentration to decrease by 50% after pseudo-equilibrium of distribution has been reached; then, terminal half-life is computed when the decrease in drug plasma concentration is due only to drug elimination, and the term 'elimination half-life' is applicable. Therefore, it is not the time necessary for the amount of the administered drug to fall by one half.
  6. ^IUPAC,Compendium of Chemical Terminology,2nd ed. (the "Gold Book" ) (1997). Online corrected version: (2006–) "Biological Half Life".doi:10.1351/goldbook.B00658
  7. ^Lin VW; Cardenas DD (2003).Spinal Cord Medicine.Demos Medical Publishing, LLC. p. 251.ISBN1-888799-61-7.
  8. ^Nordberg, Gunnar (2007).Handbook on the toxicology of metals.Amsterdam: Elsevier. p. 119.ISBN978-0-12-369413-3.
  9. ^Silk, Kenneth R.; Tyrer, Peter J. (2008).Cambridge textbook of effective treatments in psychiatry.Cambridge, UK: Cambridge University Press. p. 295.ISBN978-0-521-84228-0.
  10. ^Haberfeld H, ed. (2020).Austria-Codex(in German). Vienna: Österreichischer Apothekerverlag. Adenosin Baxter3 mg/ml Injektionslösung.
  11. ^Haberfeld H, ed. (2020).Austria-Codex(in German). Vienna: Österreichischer Apothekerverlag. Noradrenalin Orpha 1 mg/ml Konzentrat zur Herstellung einer Infusionslösung.
  12. ^Ehrsson, Hans; et al. (Winter 2002)."Pharmacokinetics of oxaliplatin in humans".Medical Oncology.19(4): 261–5.doi:10.1385/MO:19:4:261.PMID12512920.S2CID1068099.Archived fromthe originalon 28 September 2007.Retrieved28 March2007.
  13. ^ZaleplonMonograph.Accessed 15 April 2021.
  14. ^MorphineMonograph.Accessed 15 April 2021.
  15. ^abFlurazepamMonograph.Accessed 15 April 2021.
  16. ^"Trexall, Otrexup (methotrexate) dosing, indications, interactions, adverse effects, and more".reference.medscape.com.
  17. ^Manfredonia, John (March 2005)."Prescribing Methadone for Pain Management in End-of-Life Care".Journal of the American Osteopathic Association.105(3 supplement): S18-21.PMID18154194.Archived fromthe originalon 20 May 2007.Retrieved29 January2007.
  18. ^abDiazepamMonograph.Accessed 15 April 2021.
  19. ^Haberfeld H, ed. (2020).Austria-Codex(in German). Vienna: Österreichischer Apothekerverlag. Epilan D 100 mg-Tabletten.
  20. ^BuprenorphineMonograph.Accessed 15 April 2021.
  21. ^"Klonopin (clonazepam) Prescribing Guide"(PDF).Genentech USA, Inc. October 2017.Retrieved20 January2019.
  22. ^Asiri, Yousif A.; Mostafa, Gamal A.E. (2010). "Donepezil".Profiles of Drug Substances, Excipients and Related Methodology.Vol. 35. Elsevier. pp. 117–150.doi:10.1016/s1871-5125(10)35003-5.ISBN978-0-12-380884-4.ISSN1871-5125.PMID22469221.Plasma donepezil concentrations decline with a half-life of approximately 70 h. Sex, race, and smoking history have no clinically significant influence on plasma concentrations of donepezil [46–51].{{cite book}}:|journal=ignored (help)
  23. ^abFluoxetineMonograph.Accessed 15 April 2021.
  24. ^Haberfeld H, ed. (2020).Austria-Codex(in German). Vienna: Österreichischer Apothekerverlag. Sedacoron 200 mg-Tabletten.
  25. ^"Caprelsa (vandetanib) Tablets, for Oral Use. Full Prescribing Information"(PDF).Sanofi Genzyme, Cambridge, MA, Dec 2016.Retrieved24 February2020.
  26. ^Haberfeld H, ed. (2020).Austria-Codex(in German). Vienna: Österreichischer Apothekerverlag. Avodart 0,5 mg Weichkapseln.
  27. ^"Sirturo (bedaquiline) Tablets. Full Prescribing Information"(PDF).Janssen Products, Dec 2012.Retrieved24 February2020.
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  30. ^Rabinowitz et al. 1976 as cited in ATSDR 2005
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  32. ^Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 7: Neuropeptides". In Sydor A, Brown RY (eds.).Molecular Neuropharmacology: A Foundation for Clinical Neuroscience(2nd ed.). New York: McGraw-Hill Medical. p. 195.ISBN9780071481274.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.
  33. ^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.PMC2442436.PMID18475254.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)
  34. ^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.PMID22436536.S2CID25253083.
  35. ^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.PMID22467107.
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  37. ^Frymoyer, Adam (2019). "Pharmacokinetic Considerations in Neonates".Infectious Disease and Pharmacology.pp. 123–139.doi:10.1016/B978-0-323-54391-0.00011-4.ISBN9780323543910.S2CID57512164.
  38. ^Chan, Patrick; Uchizono, James A. (2015). "Pharmacokinetics and Pharmacodynamics of Anesthetics".Essentials of Pharmacology for Anesthesia, Pain Medicine, and Critical Care.pp. 3–47.doi:10.1007/978-1-4614-8948-1_1.ISBN978-1-4614-8947-4.
  39. ^abcBonate, Peter L.; Howard, Danny R. (2004).Clinical study design and analysis.Arlington, VA: AAPS Press. pp. 237–239.ISBN9780971176744.
  40. ^Toutain, P. L.; Bousquet-Melou, A. (2004). "Plasma terminal half-life".Journal of Veterinary Pharmacology and Therapeutics.27(6): 427–439.doi:10.1111/j.1365-2885.2004.00600.x.ISSN0140-7783.PMID15601438.
  41. ^Younggil Kwon (8 May 2007).Handbook of Essential Pharmacokinetics, Pharmacodynamics and Drug Metabolism for Industrial Scientists.Springer Science & Business Media. pp. 24–.ISBN978-0-306-46820-9.
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