Editing Penicillin (section)

=== Penicillin units ===
* One unit of penicillin G sodium is defined as 0.600 micrograms. Therefore, 2 million units (2 megaunits) of penicillin G is 1.2 g.<ref>{{cite web |title=Benzylpenicillin sodium 1200mg Powder for Injection |author=Genus Pharmaceuticals |website=Electronic medicines compendium |publisher=Datapharm Ltd. |date=2020-11-30 |url=https://www.medicines.org.uk/emc/product/7381/smpc |access-date=2020-12-28 |archive-date=2021-01-15 |archive-url=https://web.archive.org/web/20210115210213/https://www.medicines.org.uk/emc/product/7381/smpc |url-status=live }}</ref>
* One unit of penicillin V potassium is defined as 0.625 micrograms. Therefore 400,000 units of penicillin V is 250&nbsp;mg.<ref>{{cite web|author=Sandoz GmbH|title=Penicillin-VK|publisher=US FDA|url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/064071s006lbl.pdf|access-date=2020-12-28|archive-date=2021-01-21|archive-url=https://web.archive.org/web/20210121031128/https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/064071s006lbl.pdf|url-status=live}}</ref>

The use of units to prescribe penicillin is largely obsolete outside of the US. Since the original penicillin was an ill-defined mixture of active compounds (an amorphous yellow powder), the potency of penicillin varied from batch to batch. It was therefore impractical to prescribe 1 g of penicillin because the activity of 1 g of penicillin from one batch would be different from the activity from another batch. To address this problem, after manufacture, each batch of penicillin was standardised against a known unit of penicillin: each glass vial was then filled with the number of units required. In the 1940s, a vial of 5,000 Oxford units was standard,<ref>{{cite web |title=Penicillin, 5,000 Oxford Units |website=National Museum of American History |location=Behring Center, Washington, D.C. |url=https://americanhistory.si.edu/collections/search/object/nmah_1383607 |access-date=2020-12-28 |archive-date=2021-05-06 |archive-url=https://web.archive.org/web/20210506205630/https://americanhistory.si.edu/collections/search/object/nmah_1383607 |url-status=live }}</ref> but the depending on the batch, could contain anything from 15&nbsp;mg to 20&nbsp;mg of penicillin. Later, a vial of 1,000,000 international units became standard, and this could contain 2.5 g to 3 g of natural penicillin (a mixture of penicillin I, II, III, and IV and natural impurities). With the advent of pure penicillin G preparations (a white crystalline powder), there is little reason to prescribe penicillin in units, although units are still used for [[benzathine benzylpenicillin]] in the United States.

The "unit" of penicillin has had three previous definitions, and each definition was chosen as being roughly equivalent to the previous one.
* '''Oxford or Florey unit (1941).''' This was originally defined as the minimum amount of penicillin dissolved in 50 ml of meat extract that would inhibit the growth of a standard strain of ''Staphylococcus aureus'' (the [[Staphylococcus aureus#Standard strains|Oxford Staphylococcus]]). The reference standard was a large batch of impure penicillin kept in [[Sir William Dunn School of Pathology|Oxford]].<ref>{{cite journal | vauthors = Robinson GL | title = Penicillin in general practice | journal = Postgraduate Medical Journal | volume = 23 | issue = 256 | pages = 86–92 | date = February 1947 | pmid = 20284177 | pmc = 2529492 | doi = 10.1136/pgmj.23.256.86 }}</ref> The assay was later modified by Florey's group to a more reproducible "cup assay": in this assay, a penicillin solution was defined to contain one unit/ml of penicillin when 339 microlitres of the solution placed in a "cup" on a plate of solid agar produced a 24 millimetre zone of inhibition of growth of Oxford Staphylococcus.<ref name="Greenwood_2008">{{cite book| vauthors = Greenwood D |title=Antimicrobial Drugs: A Chronicle of a Twentieth Century Medical Triumph |date=2008 |location=Oxford, UK| publisher=Oxford University Press |page=107 |isbn=978-0-19-953484-5 }}</ref>{{rp|107}}<ref>{{cite journal | journal = Lancet | volume = 238 | issue = 6155 | pages = 177–189 | year = 1941 | title = Further observations on penicillin. | vauthors = Abraham EP, Chain E, Fletcher CM, Gardner AD, Heatley NG, Jennings MA, Florey HW | doi = 10.1016/S0140-6736(00)72122-2 }}</ref><ref name="Foster1943">{{cite journal | vauthors = Foster JW, Woodruff HB | title = Microbiological Aspects of Penicillin: I. Methods of Assay | journal = Journal of Bacteriology | volume = 46 | issue = 2 | pages = 187–202 | date = August 1943 | pmid = 16560688 | pmc = 373803 | doi = 10.1128/JB.46.2.187-202.1943 }}</ref>
* '''First International Standard (1944).''' A single 8 gram batch of pure crystalline penicillin G sodium was stored at The [[National Institute for Medical Research]] at Mill Hill in London (the International Standard). One penicillin unit was defined at 0.6 micrograms of the International Standard. An impure "working standard" was also defined and was available in much larger quantities distributed around the world: one unit of the working standard was 2.7 micrograms (the amount per unit was much larger because of the impurities). At the same time, the cup assay was refined, where instead of specifying a zone diameter of 24&nbsp;mm, the zone size were instead plotted against a reference curve to provide a readout on potency.<ref name="Foster1943"/><ref name="ScienceNews1945"/><ref name="Hartley1945">{{cite journal | vauthors = Hartley P | title = World Standard and Unit for Penicillin | journal = Science | volume = 101 | issue = 2634 | pages = 637–38 | date = June 1945 | pmid = 17844083 | doi = 10.1126/science.101.2634.637 | bibcode = 1945Sci...101..637H }}</ref>
* '''Second International Standard (1953).''' A single 30 gram batch of pure crystalline penicillin G sodium was obtained: this was also stored at Mill Hill. One penicillin unit was defined as 0.5988 micrograms of the Second International Standard.<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>

There is an older unit for penicillin V that is not equivalent to the current penicillin V unit. The reason is that the US FDA incorrectly assumed that the potency of penicillin V is the same mole-for-mole as penicillin G. In fact, penicillin V is less potent than penicillin G, and the current penicillin V unit reflects that fact.
* '''First international unit of penicillin V (1959).''' One unit of penicillin V was defined as 0.590 micrograms of a reference standard held at Mill Hill in London.<ref>{{cite journal | vauthors = Humphrey JH, Lightbown JW, Mussett MV | title = International Standard for phenoxymethylpenicillin | journal = Bulletin of the World Health Organization | volume = 20 | pages = 1221–27 | year = 1959 | issue = 6 | pmid = 14405369 | pmc = 2537888 }}</ref> This unit is now obsolete.

A similar standard was also established for penicillin K.<ref>{{cite journal | vauthors = Humphrey JH, Lightbown JW | title = The international reference preparation of penicillin K | journal = Bulletin of the World Health Organization | volume = 10 | issue = 6 | pages = 895–99 | year = 1954 | pmid = 13199652 | pmc = 2542178 }}</ref>