Biological half-life 3206099 224774407 2008-07-10T10:39:34Z Abanima 154639 interwiki {{otheruses|Half-life (disambiguation)}} The '''biological half-life''' of a substance is the time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity, as per the [[Medical Subject Headings|MeSH]] definition. Biological half-life is an important [[pharmacokinetic]] parameter and is usually denoted by the abbreviation '''''t<sub>1/2</sub>'''''.<ref>{{GoldBookRef|title=biological half life|url=http://goldbook.iupac.org/B00658.html}}</ref> 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 [[kinetics]]. See the article [[rate equation]]. {{Cleanup|date=July 2007}} ==Examples of biological half-lives== === Water === The biological half-life of water in a human is about 7 to 10 days. It can be altered by behavior. Drinking large amounts of [[alcohol]] will reduce the biological half-life of water in the body{{Fact|date=January 2007}}. This has been used to decontaminate humans who are internally contaminated with [[tritiated water]] ([[tritium]]). 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 [[Atomic Energy Research Establishment|Harwell]]) is to increase the rate at which the water in the body is replaced with new water. === Alcohol === The removal of [[ethanol]] ([[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 [[eating|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. === Prescription medications === {| class="wikitable" !Substance!!Half-life!!Notes |- |[[Amiodarone]]|| 25 days |- |[[Cisplatin]]|| 20 to 30 minutes |- |[[Chlorambucil]]|| 1.53 hours |- |[[Digoxin]]|| 24 to 36 hours |- |[[Fluoxetine]]||1 to 6 days|| The active [[metabolite]] of fluoxetine is [[lipophilic]] and migrates slowly from the brain to the blood. The metabolite has a biological half-life of 4 to 16 days. |- |[[Methadone]]||15 to 60 hours, in rare cases up to 190 hours.<ref>{{cite web |last=Manfredonia |first=John |url=http://www.jaoa.org/cgi/content/full/105/3_suppl/18S |title=Prescribing Methadone for Pain Management in End-of-Life Care | publisher=JAOA—The Journal of the American Osteopathic Association | date=March 2005 | accessdate=2007-01-29}}</ref> |- |[[Oxaliplatin]]|| 14 minutes<ref>{{cite web |last=Ehrsson |first=Hans et al |url=http://journals.humanapress.com/index.php?option=com_opbookdetails&task=articledetails&category=humanajournals&article_code=MO:19:4:261 |title=Pharmacokinetics of oxaliplatin in humans | publisher=Medical Oncology | date=Winter 2002 | accessdate=2007-03-28}}</ref> |- |[[Salbutamol]]||7 hours |- |} === Metals === 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 exchange]]r 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. 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. *[[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. ==Rate equations== ===Zero-order elimination===<!-- This section is linked from [[Sodium thiopental]] --> There are circumstances where the half-life varies with the concentration of the drug. 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 elimination). Thus the half-life, under these circumstances, is proportional to the initial concentration of the drug ''A<sub>0</sub>'' and inversely proportional to the zero-order rate constant ''k<sub>0</sub>'' where: :<math>t_{1/2} = \frac{0.5 A_{0}}{k_{0}} \,</math> ===First-order elimination=== This process is usually a logarithmic process - that is, a constant proportion of the agent is eliminated per unit time (Birkett, 2002). Thus the fall in plasma concentration after the administration of a single dose is described by the following equation: :<math>C_{t} = C_{0} e^{-kt} \,</math> *''C<sub>t</sub>'' is concentration after time ''t'' *''C<sub>0</sub>'' 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: :<math>k = \frac{\ln 2}{t_{1/2}} \,</math> Half-life is determined by [[Clearance (medicine)|clearance]] (CL) and [[volume of distribution]] (V<sub>D</sub>) and the relationship is described by the following equation: :<math>t_{1/2} = \frac{{\ln 2}.{V_D}}{CL} \,</math> In clinical practice, this means that it takes just over 4.7 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 t<sub>½</sub>) of 24-36 hours; 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 t<sub>½</sub> of about 90 days) are usually started with a [[loading dose]] to achieve their desired clinical effect more quickly. ==See also== *Browsing MeSH: **[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=mesh Entrez] **[http://www.nlm.nih.gov/mesh/MBrowser.html MeSH Browser] **GoPubMed (above) **[http://www.meshine.info/ MeSHine] **[http://www.reference.md/ Reference.MD] **[http://www.sharingpoint.net/searchOJ.asp?searchType=thesBrows SHARing Point] **[http://www.nlm.nih.gov/mesh/topsubscope2008.html List of qualifiers - 2008] * [[Half-life]], pertaining to the general mathematical concept in physics or pharmacology. * [[Kinetics]] ==References== *Birkett DJ (2002). ''Pharmacokinetics Made Easy'' (Revised Edition). Sydney: McGraw-Hill Australia. ISBN 0-07-471072-9. <references/> == External links == * [http://www.q-lead.com/adme_pk Small Molecule Drug Half-life prediction software] [[Category:Radiochemistry]] [[Category:Nuclear chemistry]] [[Category:Pharmacokinetics]] [[ar:عمر النصف الحيوي]] [[de:Plasmahalbwertszeit]] [[es:Vida media de eliminación]] [[gl:Semivida (medicina)]] [[it:Emivita (farmacologia)]] [[pt:Meia-vida biológica]] [[fi:Biologinen puoliintumisaika]] [[vi:Thời gian bán thải]] [[tr:Yarı ömür]]