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{{Short description|Pharmacological measurement unit for the amount of a biologically active substance}}
{{about-distinguish|the pharmacological unit|International System of Electrical and Magnetic Units|International System of Units|international unit of enzyme activity}}
[[File:radiance_multivitamins_nutritional_information_crop.jpg|thumb|250px|Multivitamins [[nutrition facts label]] showing that the ''international unit'' of, for example, vitamins D and E correspond to different gram values]]

In [[pharmacology]], the '''international unit''' ('''IU''') is a [[unit of measurement]] for the effect or [[biological activity]] of a substance, for the purpose of easier comparison across similar ''forms'' of substances. International units are used to quantify [[vitamin]]s and biologics ([[hormone]]s, some [[medication]]s, [[vaccine]]s, [[blood product]]s and similar biologically active substances).

International units as used in pharmacology are not part of the [[International System of Units]] (SI).<ref name=OED/> 

== For biologic preparations ==
[[File:Oxytocin intravenous bag.jpg|thumb|30 IU of oxytocin for intravenous infusion]]
[[Biologics]] are medications and other products made from biological sources. Depending on the form (powder vs solution), production method, or just batch-to-batch differences, there is often some variation in their relative potencies, so that a simple measure of [[mass]] would not suffice. The ''international unit'' allows one to compare the relative potency of all these forms, so that different forms or preparations with the same biological effect will contain the same number of IUs. To do so, the [[WHO Expert Committee on Biological Standardization]] (WHO ECBS) provides a reference preparation of the agent, arbitrarily sets the number of IUs contained in that preparation, and specifies a [[biological assay]] and/or an [[immunoassay]] procedure to compare other preparations of the same agent to the reference preparation. Since the number of IUs contained in a new substance is arbitrarily set, there is no equivalence between IU measurements of different biological agents.

=== Process of definition ===
To define the IU for a substance, an international collaborative study is organized by the [[WHO Expert Committee on Biological Standardization]] using various assay systems in several laboratories.<ref name="CSCC 1992">{{cite journal | author = Canadian Society of Clinical Chemists | title = Canadian Society of Clinical Chemists position paper: standardization of selected polypeptide hormone measurements. | journal = Clin. Biochem. | volume = 25 | issue = 6 | pages = 415–24 |date=Dec 1992 | pmid = 1477965 | doi=10.1016/0009-9120(92)90030-V}}</ref>  The main goal of the study is to reach a consensus regarding methods of analysis and the approach to standardization so that results can be compared.<ref name="Jeffcoate 1988">{{cite journal | author = Jeffcoate SL | title = What are we measuring in gonadotropin assays? | journal = Acta Endocrinol Suppl (Copenh) | volume = 288 | pages = 28–30 | year = 1988 | pmid = 3048031 }}</ref><ref name="Wicher 1991">{{cite journal | author = Wicher JT | title = Calibration is the key to immunoassay but the ideal calibrator is unattainable. | journal = Scand J Clin Lab Invest Suppl | volume = 205 | pages = 21–32 | year = 1991 | doi = 10.3109/00365519109104599 | pmid = 1947745 }}</ref><ref name="Ekins 1991">{{cite journal | author = Ekins R | title = Immunoassay standardization | journal = Scand J Clin Lab Invest Suppl | volume = 205 | pages = 33–46 | year = 1991 | doi = 10.3109/00365519109104600 | pmid = 1947747 }}</ref>

The study is performed using highly purified preparations of the [[Chemical substance|substance]], typically in [[lyophilize]]d form, called ''international reference preparations'', or ''IRPs''.<ref name="CSCC 1992" />  Each preparation is divided into precisely weighed samples, with each sample stored in its own ampoule labeled with a code corresponding to the source IRP.<ref name="CSCC 1992" />  Assays are performed using these samples and are calibrated against the previously available IU standard.  These results can be quite variable; the final IU value for samples of a given IRP are determined by consensus.<ref name="Jeffcoate 1988" />  The IRP that provides the best results and shows the best long term stability is selected to define the next IU.<ref name="CSCC 1992" />  This IRP is then referred to as the ''international standard''.<ref name="CSCC 1992" />

When a standard sample comes close to depleting, a new standard will have to be found. A new batch of the substance in question is produced and calibrated against the old one, so that the unit still represents the same amount of biological activity. Many substances have undergone several such standard sample changes. The ''third international standard'' of [[prolactin]] has nearly run out and in 2016 replacement was proposed.<ref>{{cite web |last1=Ferguson |first1=Jackie |title=WHO International Collaborative Study of the Proposed 4th International Standard for Prolactin, Human |date=2016 |url=https://www.who.int/publications/m/item/WHO-BS-2016.2292}}</ref>

=== Examples ===
* 1 IU of [[rhEGF]] is defined as the potency of 0.001 μg of a rhEGF in the "91/530" standard vial. One manufacturer reports that its rhEGF is 1.4 times as potent as the 91/530 standard.<ref name=R&D>{{cite web |title=Unit Conversion Table |url=https://www.rndsystems.com/resources/technical-information/unit-conversion-table |website=R&D Systems}}</ref>
* 12.5 IU of [[Oxytocin (medication)|oxytocin]] is defined as the potency of 21 μg of pure peptide in the "76/575" standard vial.<ref>{{cite web |title=WHO International Standard OXYTOCIN 4th International Standard NIBSC code: 76/575 Instructions for use (Version 4.0, Dated 30/04/2013) |url=https://www.nibsc.org/documents/ifu/76-575.pdf |website=nibsc.org}}</ref>

Before the purification of [[penicillin]] was perfected, the amounts were also described in "International Units" (and some non-international arbitrary "units" before them) to account for batch-to-batch variation. See {{section link|Penicillin|Penicillin units}}.

== For vitamins ==
A number of [[vitamin]]s have distinct [[vitamer]]s of distinct biological potencies. There is a system in place also called the ''international unit'' to describe the relative strength of these different molecular forms. Like the biological ''international unit'', the IU for vitamins is also an ''arbitrary'' number that cannot be interconverted among different types of activities. By 1934, the WHO (then the League of Nations Health Organisation) had already defined the international units for vitamins A, B1, C, and D.<ref name=nat1935>{{cite journal |title=Vitamin Standards |journal=Nature |date=March 1935 |volume=135 |issue=3413 |pages=516–517 |doi=10.1038/135516a0 |doi-access=free|bibcode=1935Natur.135..516. }}</ref>

Unlike biologic preparations, small molecules like vitamins can be very easily purified to yield products that are equivalent in potency. As a result, a simple mass conversion (as opposed to an assay) suffices to obtain the IU:

* 1 IU [[Vitamin A]] = 0.3 μg [[retinol]] (~0.1 nmol) = 0.6 μg beta-[[carotene]]<ref name=NIH/><ref>[http://www.hc-sc.gc.ca/fn-an/nutrition/reference/table/index-eng.php#ucf Dietary Reference Intakes Tables: Unit Conversion Factors <!-- Bot generated title -->]</ref>{{efn|The IU/RE equivalency has been replaced by the RAE conversion. See {{section link|Vitamin A|Equivalencies of retinoids and carotenoids (IU)}}.<ref name=NIH/>}}
* 1 IU [[Vitamin D]] = 0.025&nbsp;μg D<sub>2</sub>/D<sub>3</sub> ≈ 0.65 pmol<ref>{{cite web |title=Vitamin D: Fact Sheet for Health Professionals |url=https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/ |access-date=6 January 2018}}</ref>
* 1 IU [[Vitamin E]] = {{frac|2|3}} [[milligram|mg]] d-[[alpha-tocopherol]] = 0.90&nbsp;mg of dl-alpha-[[tocopherol]]<ref name=NIH>{{cite web |title=Unit Conversions |url=https://dietarysupplementdatabase.usda.nih.gov/Conversions.php |publisher=[[National Institutes of Health]] |access-date=2018-11-21 |archive-date=2021-04-27 |archive-url=https://web.archive.org/web/20210427102806/https://dietarysupplementdatabase.usda.nih.gov/Conversions.php |url-status=dead }}</ref>{{efn|The US NIH has replaced IU with mg d-alpha-tocopherol equiv. See {{section link|Vitamin E|Food labeling}}.<ref name=NIH/>}}

== History ==
{{missing information|section|what the early biologic standards look like; when did the vitamin A IU receive a conversion for retinol|date=December 2023}}
In 1931, the Permanent Commission on Biological Standardisation of the League of Nations Health Organisation specified the provisional standards for vitamins A, B1, C, and D. These original standards were quite crude by modern measures: the standard for vitamin A was a mixture of many carotenoids,<ref>{{cite journal |title=Standardisation and Estimation of Vitamin A |journal=The Lancet |date=December 1935 |volume=226 |issue=5858 |pages=1307 |doi=10.1016/S0140-6736(00)47376-9 }}</ref> for vitamin B<sub>1</sub> the result of adsorbing rice polishings onto [[fuller's earth]], for vitamin C a sample of lemon juice, for vitamin D a sample of irradiated ergosterol in oil. In 1935, the standards for A, C, and D were changed to use pure substances: pure beta-carotene in oil, crystalline [[ascorbic acid]], and crystalline [[ergocalciferol]].<ref name=nat1935/> This same commission also established early standards for biologics ([[antitoxins]], insulins, pituitary extract and sex hormones) in the [[interwar period]].<ref name=Pen1945>{{cite journal |last1=Hartley |first1=Percival |title=World Standard and Unit for Penicillin |journal=Science |date=22 June 1945 |volume=101 |issue=2634 |pages=637–638 |doi=10.1126/science.101.2634.637|pmid=17844083 |bibcode=1945Sci...101..637H }}</ref>

In 1944, officials from the League of Nations, in cooperation with the Royal Society, established a first international standard for [[penicillin]].<ref name=Pen1945/> The postwar World Health Organization established a second standard in 1953. Both were defined using a pure, crystalline substance.<ref>{{cite journal | vauthors = Humphrey JH, Musset MV, Perry WL | title = The second international standard for penicillin | journal = Bulletin of the World Health Organization | volume = 9 | issue = 1 | pages = 15–28 | year = 1953 | pmid = 13082387 | pmc = 2542105 }}</ref>

{{missing information|section|later standardization of larger biomolecules; bioassays vs immunoassays|date=December 2023}}

== Languages ==
The name ''international unit'' is often capitalized in English and other languages, although major English-language dictionaries treat it as a common noun and thus use lower case.<ref name=OED>{{Cite OED|international unit}}</ref> The name has several accepted abbreviations. It is usually abbreviated as ''IU'' in English, and ''UI'' in [[Romance languages]] (for example [[Spanish language|Spanish]] ''unidad internacional'', [[Portuguese language|Portuguese]] ''unidade internacional'', [[French language|French]] ''unité internationale'', [[Italian language|Italian]] ''unità internazionale'', [[Romanian language|Romanian]] ''unitate internațională''), ''IE'' in several [[Germanic languages]] (for example [[German language|German]] ''internationale Einheit'', [[Dutch language|Dutch]] ''internationale eenheid'') or as other forms (for example [[Russian language|Russian]] '''МЕ''', международная единица [''mezhdunarodnaya yedinitsa''], [[Hungarian language|Hungarian]] '''NE''', ''nemzetközi egység'').{{cn|date=August 2022}}

In order to remove the possibility of having the letter "I" confused with the digit "1", some hospitals have it as a stated policy omit the "I", that is, to only use '''U''' or '''E''' when talking and writing about dosages, while other hospitals require the word "units" (or words "international units") to be written out entirely.<ref name=JCAHO>{{cite web|url=http://www.jointcommission.org/assets/1/18/Do_Not_Use_List.pdf |title=Facts about the Official "Do Not Use" List |publisher=The Joint Commission |access-date=30 May 2013 |url-status=dead |archive-url=https://web.archive.org/web/20130310233725/http://www.jointcommission.org/assets/1/18/Do_Not_Use_List.pdf |archive-date=March 10, 2013 }}</ref>  (For example, "three international units per litre" may be abbreviated "3&nbsp;U/L". The "liter" sign (L) is less affected, as [[Litre#Symbol|less confusing written forms are used]].)

==See also==
* ''[[United States Pharmacopeia]]'' (''USP'')

==References==
===Notes===
{{notelist}}

===Citations===
{{Reflist|25em}}

==External links==
{{wiktionary}}
* [https://www.who.int/biologicals/reference_preparations/en/ WHO reference preparations]
* [https://mypharmatools.com/othertools/iu Online converter with authoritative references for all substances]

League of Nations archives:
* [https://archives.ungeneva.org/standardisation-of-biological-products Sub-sub-series R850-R852/12B/26142 - Standardisation of Biological Products] - UN Geneva archives
* [https://archives.ungeneva.org/permanent-commission-on-biological-standardisation Sub-sub-series R6214-R6216/8E/2887 - Permanent Commission on Biological Standardisation] - UN Geneva archives
* [https://digital.nls.uk/league-of-nations/archive/193055612 Bulletin of the Health Organization], volumes 6&ndash;11 - National Library of Scotland

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[[Category:Units of measurement]]
[[Category:Dosage forms]]