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 patients who are internally contaminated with tritiated water. The basis of this decontamination method is to increase the rate at which the water in the body is replaced with new water.
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 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.
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, 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.
Half-times apply to processes where the elimination rate is exponential. If
C
(
t
)
{\displaystyle C(t)}
is the concentration of a substance at time
t
{\displaystyle t}
, its time dependence is given by
C
(
t
)
=
C
(
0
)
e
−
k
t
{\displaystyle C(t)=C(0)e^{-kt}\,}
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 t1/2 of about 58 days) are usually started with a loading dose to achieve their desired clinical effect more quickly.
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.
"Elimination Half-Life". Pharmacology in one semester. Archived from the original on 22 October 2020. Retrieved 20 February 2020. https://web.archive.org/web/20201022081736/https://sites.google.com/site/pharmacologyinonesemester/2-drug-distribution-metabolism-and-elimination/2-5-blood-levels/2-5-2-elimination-half-life
"Definition of Half-Life (t1⁄2)". AIDSinfo. 19 February 2020. Archived from the original on 20 February 2020. Retrieved 20 February 2020. https://web.archive.org/web/20200220040435/https://aidsinfo.nih.gov/understanding-hiv-aids/glossary/286/half-life
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. ISBN 978-0-12-079035-7. The elimination half-life measures the kinetics of loss of drug from the body as a whole once all distribution equilibria have been achieved. 978-0-12-079035-7
Dasgupta, 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. ISBN 978-0-12-815849-4. S2CID 209258489. 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. 978-0-12-815849-4
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. PMID 15601438. Archived from the 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. https://web.archive.org/web/20200220042629/http://physiologie.envt.fr/wp-content/uploads/2016/06/Plasma_terminal_half-life.pdf
"Definition of Half-Life (t1⁄2)". AIDSinfo. 19 February 2020. Archived from the original on 20 February 2020. Retrieved 20 February 2020. https://web.archive.org/web/20200220040435/https://aidsinfo.nih.gov/understanding-hiv-aids/glossary/286/half-life
Dasgupta, 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. ISBN 978-0-12-815849-4. S2CID 209258489. 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. 978-0-12-815849-4
IUPAC, Compendium of Chemical Terminology, 2nd ed. (the "Gold Book") (1997). Online corrected version: (2006–) "Biological Half Life". doi:10.1351/goldbook.B00658 /wiki/International_Union_of_Pure_and_Applied_Chemistry
Lin VW; Cardenas DD (2003). Spinal Cord Medicine. Demos Medical Publishing, LLC. p. 251. ISBN 1-888799-61-7. 1-888799-61-7
Nordberg, Gunnar (2007). Handbook on the toxicology of metals. Amsterdam: Elsevier. p. 119. ISBN 978-0-12-369413-3. 978-0-12-369413-3
Silk, Kenneth R.; Tyrer, Peter J. (2008). Cambridge textbook of effective treatments in psychiatry. Cambridge, UK: Cambridge University Press. p. 295. ISBN 978-0-521-84228-0. 978-0-521-84228-0
Haberfeld H, ed. (2020). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag. Adenosin Baxter3 mg/ml Injektionslösung.
Haberfeld H, ed. (2020). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag. Noradrenalin Orpha 1 mg/ml Konzentrat zur Herstellung einer Infusionslösung.
Ehrsson, Hans; et al. (Winter 2002). "Pharmacokinetics of oxaliplatin in humans". Medical Oncology. 19 (4): 261–5. doi:10.1385/MO:19:4:261. PMID 12512920. S2CID 1068099. Archived from the original on 28 September 2007. Retrieved 28 March 2007. https://web.archive.org/web/20070928104657/http://journals.humanapress.com/index.php?option=com_opbookdetails&task=articledetails&category=humanajournals&article_code=MO%3A19%3A4%3A261
Zaleplon Monograph. Accessed 15 April 2021. https://www.drugs.com/monograph/zaleplon.html
Morphine Monograph. Accessed 15 April 2021. https://www.drugs.com/monograph/morphine.html
Flurazepam Monograph. Accessed 15 April 2021. https://www.drugs.com/monograph/flurazepam.html
Flurazepam Monograph. Accessed 15 April 2021. https://www.drugs.com/monograph/flurazepam.html
"Trexall, Otrexup (methotrexate) dosing, indications, interactions, adverse effects, and more". reference.medscape.com. http://reference.medscape.com/drug/trexall-methotrexate-343201#showall
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. PMID 18154194. Archived from the original on 20 May 2007. Retrieved 29 January 2007. https://web.archive.org/web/20070520062222/http://www.jaoa.org/cgi/content/full/105/3_suppl/18S
Diazepam Monograph. Accessed 15 April 2021. https://www.drugs.com/monograph/diazepam.html
Diazepam Monograph. Accessed 15 April 2021. https://www.drugs.com/monograph/diazepam.html
Haberfeld H, ed. (2020). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag. Epilan D 100 mg-Tabletten.
Buprenorphine Monograph. Accessed 15 April 2021. https://www.drugs.com/monograph/buprenorphine.html
"Klonopin (clonazepam) Prescribing Guide" (PDF). Genentech USA, Inc. October 2017. Retrieved 20 January 2019. https://www.gene.com/download/pdf/klonopin_prescribing.pdf
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. ISBN 978-0-12-380884-4. ISSN 1871-5125. PMID 22469221. 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) 978-0-12-380884-4
Fluoxetine Monograph. Accessed 15 April 2021. https://www.drugs.com/monograph/fluoxetine.html
Fluoxetine Monograph. Accessed 15 April 2021. https://www.drugs.com/monograph/fluoxetine.html
Haberfeld H, ed. (2020). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag. Sedacoron 200 mg-Tabletten.
"Caprelsa (vandetanib) Tablets, for Oral Use. Full Prescribing Information" (PDF). Sanofi Genzyme, Cambridge, MA, Dec 2016. Retrieved 24 February 2020. http://www.caprelsa.com/files/caprelsa-pi.pdf
Haberfeld H, ed. (2020). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag. Avodart 0,5 mg Weichkapseln.
"Sirturo (bedaquiline) Tablets. Full Prescribing Information" (PDF). Janssen Products, Dec 2012. Retrieved 24 February 2020. https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/204384s000lbl.pdf
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): RA329-36. PMID 16192916. http://www.medscimonit.com/abstract/index/idArt/430340
Griffin et al. 1975 as cited in ATSDR 2005
Rabinowitz et al. 1976 as cited in ATSDR 2005
Baribeau, Danielle A; Anagnostou, Evdokia (2015). "Oxytocin and vasopressin: linking pituitary neuropeptides and their receptors to social neurocircuits". Frontiers in Neuroscience. 9: 335. doi:10.3389/fnins.2015.00335. ISSN 1662-453X. PMC 4585313. PMID 26441508. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4585313
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. 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. 9780071481274
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 2442436. 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) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2442436
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. S2CID 25253083. /wiki/Psychoneuroendocrinology_(journal)
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. /wiki/Neuro_Endocrinology_Letters
Baribeau, Danielle A; Anagnostou, Evdokia (2015). "Oxytocin and vasopressin: linking pituitary neuropeptides and their receptors to social neurocircuits". Frontiers in Neuroscience. 9: 335. doi:10.3389/fnins.2015.00335. ISSN 1662-453X. PMC 4585313. PMID 26441508. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4585313
Miles Hacker; William S. Messer; Kenneth A. Bachmann (19 June 2009). Pharmacology: Principles and Practice. Academic Press. p. 205. ISBN 978-0-08-091922-5. 978-0-08-091922-5
Frymoyer, Adam (2019). "Pharmacokinetic Considerations in Neonates". Infectious Disease and Pharmacology. pp. 123–139. doi:10.1016/B978-0-323-54391-0.00011-4. ISBN 9780323543910. S2CID 57512164. 9780323543910
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. ISBN 978-1-4614-8947-4. 978-1-4614-8947-4
Bonate, Peter L.; Howard, Danny R. (2004). Clinical study design and analysis. Arlington, VA: AAPS Press. pp. 237–239. ISBN 9780971176744. 9780971176744
Bonate, Peter L.; Howard, Danny R. (2004). Clinical study design and analysis. Arlington, VA: AAPS Press. pp. 237–239. ISBN 9780971176744. 9780971176744
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. ISSN 0140-7783. PMID 15601438. /wiki/Doi_(identifier)
Younggil Kwon (8 May 2007). Handbook of Essential Pharmacokinetics, Pharmacodynamics and Drug Metabolism for Industrial Scientists. Springer Science & Business Media. pp. 24–. ISBN 978-0-306-46820-9. 978-0-306-46820-9
Bonate, Peter L.; Howard, Danny R. (2004). Clinical study design and analysis. Arlington, VA: AAPS Press. pp. 237–239. ISBN 9780971176744. 9780971176744