Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and Phenoxymethylpenicillin: Difference between pages

{{Short description|Antibiotic medication}}

{{Use dmy dates|date=January 2024}}

{{cs1 config |name-list-style=vanc |display-authors=6}}

{{Infobox drug

| verifiedrevid = 464200689

| image = Penicillin-V-2D-skeletal.svg

| alt =

| image2 = Phenoxymethylpenicillin-from-xtal-3D-bs-17.png

| alt2 =

| caption =

<!-- Clinical data -->

| pronounce =

| tradename = Veetids, Apocillin,<ref>{{cite web |url=https://www.felleskatalogen.no/medisin/apocillin-actavis-546118 |title=Apocillin |language=no |work=Felleskatalogen |publisher=LMI (Legemiddelindustrien) |access-date=23 June 2018 |quote=fenoksymetylpenicillin }}</ref> others

| DailyMedID = Penicillin V

| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->

| pregnancy_AU_comment =

| pregnancy_category =

| routes_of_administration = [[oral administration|By mouth]]

| class =

| ATC_prefix = J01

| ATC_suffix = CE02

| ATC_supplemental =

<!-- Legal status -->

| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled -->

| legal_AU_comment =

| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->

| legal_BR_comment =

| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->

| legal_CA_comment =

| legal_DE = <!-- Anlage I, II, III or Unscheduled -->

| legal_DE_comment =

| legal_NZ = <!-- Class A, B, C -->

| legal_NZ_comment =

| legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM / Class A, B, C -->

| legal_UK_comment =

| legal_US = Rx-only

| legal_US_comment =

| legal_EU =

| legal_EU_comment =

| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->

| legal_UN_comment =

<!-- Pharmacokinetic data -->

| metabolism = [[Liver]]

| metabolites =

| onset =

| duration_of_action =

| excretion = [[Kidney]]

<!-- Identifiers -->

| CAS_supplemental = {{CAS|132-98-9}} (potassium), {{CAS|147-48-8}} (anhydrous calcium), {{CAS|73368-74-8}} (calcium dihydrate)

| IUPHAR_ligand =

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| UNII_Ref = {{fdacite|correct|FDA}}

| ChEBI_Ref = {{ebicite|correct|EBI}}

| ChEBI = 27446

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| NIAID_ChemDB =

| PDB_ligand =

| synonyms = penicillin phenoxymethyl, penicillin V, penicillin VK

<!-- Chemical and physical data -->

| IUPAC_name = 3,3-Dimethyl-7-oxo-6-(2-phenoxyacetamido)-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid

| C=16 | H=18 | N=2 | O=5 | S=1

| SMILES = CC1([C@@H](N2[C@H](S1)[C@@H](C2=O)NC(=O)COC3=CC=CC=C3)C(=O)O)C

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 1S/C16H18N2O5S/c1-16(2)12(15(21)22)18-13(20)11(14(18)24-16)17-10(19)8-23-9-6-4-3-5-7-9/h3-7,11-12,14H,8H2,1-2H3,(H,17,19)(H,21,22)/t11-,12+,14-/m1/s1

| StdInChI_comment =

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = BPLBGHOLXOTWMN-MBNYWOFBSA-N

| density =

| density_notes =

| melting_point = 120-128

| melting_high =

| melting_notes =

| boiling_point =

| boiling_notes =

| solubility =

| sol_units =

| specific_rotation =

<!-- Definition and medical uses -->

'''Phenoxymethylpenicillin''', also known as '''penicillin V''' ('''PcV''') and '''penicillin VK''', is an [[antibiotic]] useful for the treatment of a number of [[bacterial infections]].<ref name="WHO2008" /> Specifically it is used for the treatment of [[strep throat]], [[otitis media]], and [[cellulitis]].<ref name="WHO2008" /> It is also used to prevent [[rheumatic fever]] and to prevent infections following [[splenectomy|removal of the spleen]].<ref name="WHO2008" /> It is given by mouth.<ref name="WHO2008">{{cite book | title = WHO Model Formulary 2008 | year = 2009 | isbn = 9789241547659 | vauthors = ((World Health Organization)) | veditors = Stuart MC, Kouimtzi M, Hill SR | hdl = 10665/44053 | author-link = World Health Organization | publisher = World Health Organization | hdl-access=free }}</ref>

<!-- Side effects and mechanism -->

Side effects include [[diarrhea]], [[nausea]], and [[allergic reaction]]s including [[anaphylaxis]].<ref name=WHO2008/> It is not recommended in those with a history of [[penicillin allergy]].<ref name=WHO2008/> It is relatively safe for use during [[pregnancy]].<ref name=Ric2015>{{cite book| vauthors = Hamilton R |title=Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition|date=2015|publisher=Jones & Bartlett Learning|isbn=9781284057560|page=95}}</ref> It is in the [[penicillin]] and [[beta lactam]] family of medications.<ref name=AHFS2016/> It usually results in [[bactericidal|bacterial death]].<ref name=AHFS2016/>

<!-- History and culture -->

Phenoxymethylpenicillin was first made in 1948 by [[Eli Lilly and Company|Eli Lilly]].<ref name="Greenwood2008">{{cite book| vauthors = Greenwood D | chapter = Wonder Drugs |title=Antimicrobial Drugs: Chronicle of a Twentieth Century Medical Triumph|date=2008|publisher=OUP Oxford|isbn=978-0-19-953484-5| chapter-url = https://books.google.com/books?id=i4_FZHmzjzwC&pg=PA121|language=en|url-status=live|archive-url=https://web.archive.org/web/20161220084325/https://books.google.ca/books?id=i4_FZHmzjzwC&pg=PA121|archive-date=20 December 2016}}</ref>{{rp|121}} It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref> It is available as a [[generic medication]].<ref name=AHFS2016>{{cite web|title=Penicillin V|url=https://www.drugs.com/monograph/penicillin-v.html|publisher=The American Society of Health-System Pharmacists|access-date=8 December 2016|url-status=live|archive-url=https://web.archive.org/web/20161220230657/https://www.drugs.com/monograph/penicillin-v.html|archive-date=20 December 2016}}</ref> In 2021, it was the 256th most commonly prescribed medication in the United States, with more than 1{{nbsp}}million prescriptions.<ref>{{cite web | title=The Top 300 of 2021 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=14 January 2024 | archive-date=15 January 2024 | archive-url=https://web.archive.org/web/20240115223848/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Penicillin V - Drug Usage Statistics | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/PenicillinV | access-date = 14 January 2024}}</ref>

== Medical uses ==

Specific uses for phenoxymethylpenicillin include:<ref name="Martindale"/><ref name="AMH2006">{{cite book | editor=Rossi S. | title=Australian Medicines Handbook | year=2006 | location=Adelaide | publisher=Australian Medicines Handbook Pty Ltd| isbn=0-9757919-2-3| title-link=Australian Medicines Handbook }}</ref>

* Infections caused by ''[[Streptococcus pyogenes]]''

** [[Tonsillitis]]

** [[Pharyngitis]]

** [[Skin]] infections

* [[Anthrax]] (mild uncomplicated infections)

* [[Lyme disease]] (early stage in pregnant women or young children)

* [[Rheumatic fever]] (primary and secondary prophylaxis)

* [[Streptococcus|Streptococcal]] skin infections

* [[Spleen#Disorders|Spleen disorders]] (pneumococcal infection prophylaxis)

* Initial treatment for dental abscesses

* Moderate-to-severe [[gingivitis]] (with [[metronidazole]])

* [[Avulsion injuries]] of teeth (as an alternative to tetracycline)

* Blood infection prophylaxis in children with [[sickle cell disease]].

Penicillin V is sometimes used in the treatment of [[wikt:odontogenic|odontogenic]] infections.{{cn|date=March 2023}}

It is less active than [[benzylpenicillin]] (penicillin G) against [[Gram-negative bacteria]].<ref name="Garrod1960">

{{cite journal | vauthors = Garrod LP | title = Relative antibacterial activity of three penicillins | journal = British Medical Journal | volume = 1 | issue = 5172 | pages = 527–529 | date = February 1960 | pmid = 13826674 | pmc = 1966560 | doi = 10.1136/bmj.1.5172.527 }}</ref><ref name="Garrod1960a">

{{cite journal | vauthors = Garrod LP | title = The relative antibacterial activity of four penicillins | journal = British Medical Journal | volume = 2 | issue = 5214 | pages = 1695–1696 | date = December 1960 | pmid = 13703756 | pmc = 2098302 | doi = 10.1136/bmj.2.5214.1695 }}</ref> Phenoxymethylpenicillin has a range of antimicrobial activity against [[Gram-positive bacteria]] that is similar to that of benzylpenicillin and a similar mode of action, but it is substantially less active than benzylpenicillin against [[Gram-negative bacteria]].<ref name="Garrod1960" /><ref name="Garrod1960a" />

Phenoxymethylpenicillin is more acid-stable than benzylpenicillin, which allows it to be given orally.{{cn|date=March 2023}}

Phenoxymethylpenicillin is usually used only for the treatment of mild to moderate infections, and not for severe or deep-seated infections since [[Absorption (pharmacokinetics)|absorption]] can be unpredictable. Except for the treatment or prevention of infection with ''[[Streptococcus pyogenes]]'' (which is uniformly sensitive to penicillin), therapy should be guided by bacteriological studies (including sensitivity tests) and by clinical response.<ref name="DailyMed"/> People treated initially with [[parenteral]] benzylpenicillin may continue treatment with phenoxymethylpenicillin by mouth once a satisfactory response has been obtained.<ref name="Martindale">{{cite book|editor=Sweetman S.|title=Martindale: The complete drug reference|publisher=Royal Pharmaceutical Society of Great Britain and the Pharmaceutical Press|location=London|year=2002|edition=Electronic version}}</ref>

It is not active against [[beta-lactamase]]-producing bacteria, which include many strains of ''[[staphylococcus|Staphylococci]]''.<ref name="DailyMed">{{cite web|url=http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=645|title=Penicillin V Potassium tablet: Drug Label Sections|date=December 2006|publisher=[[United States National Library of Medicine|U.S. National Library of Medicine]], [[Daily Med]]: Current Medication Information|access-date=2 August 2009|url-status=live|archive-url=https://web.archive.org/web/20090727065618/http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=645|archive-date=27 July 2009}}</ref>

== Adverse effects ==

{{further|Penicillin drug reaction}}

Phenoxymethylpenicillin is usually well tolerated but may occasionally cause transient [[nausea]], vomiting, epigastric distress, [[diarrhea]], constipation, acidic smell to urine and [[black hairy tongue]]. A previous [[hypersensitivity|hypersensitivity reaction]] to ''any'' [[penicillin]] is a [[contraindication]].<ref name="Martindale"/><ref name="DailyMed"/>

==Mechanism of action==

{{further|Penicillin#Mechanism of action}}

The mechanism of phenoxymethylpenicillin is identical to that of all other penicillins. It exerts a [[Bactericidal#Bactericidal antibiotics|bactericidal]] action against penicillin-sensitive microorganisms during the stage of active multiplication. It acts by [[enzyme inhibitor|inhibiting]] the [[protein biosynthesis|biosynthesis]] of cell-wall [[peptidoglycan]].<ref>{{cite journal | vauthors = Yocum RR, Rasmussen JR, Strominger JL | title = The mechanism of action of penicillin. Penicillin acylates the active site of Bacillus stearothermophilus D-alanine carboxypeptidase | journal = The Journal of Biological Chemistry | volume = 255 | issue = 9 | pages = 3977–3986 | date = May 1980 | pmid = 7372662 | doi = 10.1016/S0021-9258(19)85621-1 | doi-access = free }}</ref>

== Compendial status ==

* [[British Pharmacopoeia]]<ref name=ibp2009>{{cite web| work =British Pharmacopoeia Commission Secretariat| title =Index (BP 2009)| url =http://www.pharmacopoeia.co.uk/pdf/2009_index.pdf| access-date =26 March 2010| url-status =dead| archive-url =https://web.archive.org/web/20090411071437/http://www.pharmacopoeia.co.uk/pdf/2009_index.pdf| archive-date =11 April 2009}}</ref>

==History==

The Austrian pharmaceutical company, Biochemie, was founded in [[Kundl]] in July 1946 at the site of a derelict brewery, at the suggestion of a French officer, Michel Rambaud (a chemist), who was able to obtain a small amount of ''Penicillium'' start culture from France. Contamination of the fermentation tanks was a persistent problem and in 1951, the company biologist, [[Ernst Brandl]], attempted to solve this by adding [[phenoxyethanol]] to the tanks as an anti-bacterial disinfectant. This resulted unexpectedly in an increase in penicillin production: but, the penicillin produced was not benzylpenicillin, but phenoxymethylpenicillin. Phenoxyethanol was fermented to [[phenoxyacetic acid]]<ref>{{cite web|title=Phenoxyacetic acid |website=PubChem |publisher=National Center for Biotechnology Information, National Library of Medicine |url=https://pubchem.ncbi.nlm.nih.gov/compound/Phenoxyacetic-acid |date=26 December 2020 |access-date=1 January 2021 |location=Bethesda, MD, USA }}</ref> in the tanks, which was then incorporated into penicillin via biosynthesis. Importantly, Brandl realised that phenoxymethylpenicillin is not destroyed by stomach acid and can therefore be given by mouth. Phenoxymethyl penicillin was originally discovered by Eli Lilly in 1948 as part of their efforts to study penicillin precursors, but was not further exploited, and there is no evidence that Lilly understood the significance of their discovery at the time.<ref name="Greenwood2008"/>{{rp|119–121}}<ref>{{cite journal | vauthors = Behrens OK, Corse J | title = Biosynthesis of penicillins; biological precursors for benzylpenicillin (penicillin G) | journal = The Journal of Biological Chemistry | volume = 175 | issue = 2 | pages = 751–764 | date = September 1948 | pmid = 18880772 | doi = 10.1016/S0021-9258(18)57194-5 | doi-access = free }}</ref>

Biochemie is part of [[Novartis#Sandoz|Sandoz]].{{cn|date=January 2024}}

== Society and culture ==

=== Names ===

There were four named penicillins at the time penicillin V was discovered ([[Penicillin#Nomenclature|penicillins I, II, III, IV]]), however, Penicillin V was named "V" for ''Vertraulich'' (German for ''confidential'');<ref name="Greenwood2008"/>{{rp|121}} it was not named for the Roman numeral "5".

Penicillin VK is the [[potassium]] salt of penicillin V (K is the chemical symbol for potassium).{{cn|date=March 2023}}

== References ==

{{reflist}}

{{PenicillinAntiBiotics}}

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[[Category:Penicillins]]

[[Category:Enantiopure drugs]]

[[Category:World Health Organization essential medicines]]

[[Category:Wikipedia medicine articles ready to translate]]

[[Category:Drugs developed by Eli Lilly and Company]]