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Revision as of 09:36, 21 November 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Saving copy of the {{drugbox}} taken from revid 461676886 of page Pyrazinamide for the Chem/Drugbox validation project (updated: 'DrugBank').  Latest revision as of 05:51, 23 December 2024 edit Whywhenwhohow (talk | contribs)Autopatrolled, Extended confirmed users, Pending changes reviewers49,132 edits infobox 
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{{Short description|Medication}}
{{ambox | text = This page contains a copy of the infobox ({{tl|drugbox}}) taken from revid of page ] with values updated to verified values.}}
{{Use dmy dates|date=May 2024}}
{{Drugbox {{Drugbox
| verifiedrevid = 461741379
| Verifiedfields = changed
| verifiedrevid = 417854855
| IUPAC_name = pyrazine-2-carboxamide
| image = Pyrazinamide.svg | image = Pyrazinamide.svg
| width = 120 | width = 120
| alt =
| image2 = Pyrazinamide ball-and-stick.png
| width2 = 200
| alt2 =


<!--Clinical data--> <!--Clinical data-->
| tradename = Rifater | tradename = Rifater, Tebrazid, others<ref name=Ric2015/>
| Drugs.com = {{drugs.com|monograph|pyrazinamide}} | Drugs.com = {{drugs.com|monograph|pyrazinamide}}
| MedlinePlus = a682402 | MedlinePlus = a682402
| DailyMedID = Pyrazinamide
| pregnancy_category = C
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| legal_status = ?
| pregnancy_AU_comment =
| routes_of_administration = Oral
| pregnancy_category =
| routes_of_administration = ]
| ATC_prefix = J04
| ATC_suffix = AK01
| ATC_supplemental = {{ATC|J04|AM09}}, {{ATC|J04|AM10}}, {{ATC|J04|AM11}}, {{ATC|J04|AM12}}

<!-- 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_UN = <!-- N I, II, III, IV / P I, II, III, IV-->
| legal_UN_comment =
| legal_status = Rx-only


<!--Pharmacokinetic data--> <!--Pharmacokinetic data-->
| bioavailability = &gt;90% | bioavailability = &gt;90%
| metabolism = ] | metabolism = ]
| elimination_half-life = 9 to 10 hours | elimination_half-life = 9 to 10 hours
| excretion = ] | excretion = ]


<!--Identifiers--> <!--Identifiers-->
| IUPHAR_ligand = 7287
| CASNo_Ref = {{cascite|correct|CAS}}
| CAS_number_Ref = {{cascite|correct|??}} | CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 98-96-4 | CAS_number = 98-96-4
| ATC_prefix = J04
| ATC_suffix = AK01
| PubChem = 1046 | PubChem = 1046
| DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank_Ref = {{drugbankcite|correct|drugbank}}
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| KEGG_Ref = {{keggcite|correct|kegg}} | KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00144 | KEGG = D00144
| ChEBI_Ref = {{ebicite|changed|EBI}} | ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 45285 | ChEBI = 45285
| ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 614 | ChEMBL = 614
| NIAID_ChemDB = 007697

<!--Chemical data--> <!--Chemical data-->
| IUPAC_name = pyrazine-2-carboxamide
| C=5 | H=5 | N=3 | O=1
| C=5 | H=5 | N=3 | O=1
| molecular_weight = 123.113 g/mol
| smiles = O=C(N)c1nccnc1 | smiles = O=C(N)c1nccnc1
| InChI = 1/C5H5N3O/c6-5(9)4-3-7-1-2-8-4/h1-3H,(H2,6,9)
| InChIKey = IPEHBUMCGVEMRF-UHFFFAOYAZ
| StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C5H5N3O/c6-5(9)4-3-7-1-2-8-4/h1-3H,(H2,6,9) | StdInChI = 1S/C5H5N3O/c6-5(9)4-3-7-1-2-8-4/h1-3H,(H2,6,9)
Line 52: Line 75:
| StdInChIKey = IPEHBUMCGVEMRF-UHFFFAOYSA-N | StdInChIKey = IPEHBUMCGVEMRF-UHFFFAOYSA-N
}} }}

<!-- Definition and medical uses -->
'''Pyrazinamide''' is a medication used to treat ].<ref name=AHFS2016/> For active tuberculosis, it is often used with ], ], and either ] or ].<ref name=WHO2008>{{cite book | title = WHO Model Formulary | year = 2009 | isbn = 978-9241547659 | 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 |pages=136, 140, 594, 608 }}</ref> It is not generally recommended for the treatment of latent tuberculosis.<ref name=AHFS2016/> It is taken ].<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=415}}</ref>

<!-- Side effects and mechanism -->
Common side effects include nausea, loss of appetite, muscle and joint pains, and rash.<ref name=AHFS2016/><ref name=":2">{{Cite book|title=Medical-surgical nursing : assessment and management of clinical problems| vauthors = Lewis SM, Dirksen SR, Heitkemper MM, Bucher L, Harding M |date=5 December 2013|isbn=978-0-323-10089-2|edition=9th| publisher = Mosby |location=St. Louis, MO|oclc=228373703}}</ref> More serious side effects include ], ], and sensitivity to sunlight.<ref name=AHFS2016/> It is not recommended in those with significant liver disease or ].<ref name=WHO2008/> It is unclear if use during ] is safe but it is likely okay during ].<ref name=WHO2008/> Pyrazinamide is in the ] class of medications.<ref name=AHFS2016/> How it works is not entirely clear.<ref name=AHFS2016/>

<!-- History and culture -->
Pyrazinamide was first made in 1936, but did not come into wide use until 1972.<ref>{{cite book| vauthors = Donald PR, van Helden PD |title=Antituberculosis Chemotherapy |date=2011 |publisher=Karger Medical and Scientific Publishers |isbn=978-3805596282 |page=8 |url= https://books.google.com/books?id=aZc7AQAAQBAJ&pg=PA8|language=en|url-status=live|archive-url= https://web.archive.org/web/20170910172352/https://books.google.com/books?id=aZc7AQAAQBAJ&pg=PA8 |archive-date=10 September 2017}}</ref> It is on the ].<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list | 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> Pyrazinamide is available as a generic medication.<ref name=AHFS2016>{{cite web|title=Pyrazinamide|url=https://www.drugs.com/monograph/pyrazinamide.html|publisher=The American Society of Health-System Pharmacists|access-date=8 December 2016|url-status=live|archive-url=https://web.archive.org/web/20161220231056/https://www.drugs.com/monograph/pyrazinamide.html|archive-date=20 December 2016}}</ref>

== Medical uses ==
Pyrazinamide is only used in combination with other drugs such as isoniazid and rifampicin in the ] of '']'' and as ] (DOT).<ref name=":2" /> It is never used on its own. It has no other ]. In particular, it is not used to treat other ]; '']'' and '']'' are innately resistant to pyrazinamide.

Pyrazinamide is used in the first 2 months of treatment to reduce the duration of treatment required.<ref name="MRC">{{cite journal | vauthors = | title = Controlled trial of four thrice-weekly regimens and a daily regimen all given for 6 months for pulmonary tuberculosis | journal = Lancet | volume = 1 | issue = 8213 | pages = 171–174 | date = January 1981 | pmid = 6109855 | doi = 10.1016/S0140-6736(02)95623-0 }}</ref> Regimens not containing pyrazinamide must be taken for 9 months or more.

Pyrazinamide is a potent ] drug<ref name="pmid10716583">{{cite journal | vauthors = Spaia S, Magoula I, Tsapas G, Vayonas G | title = Effect of pyrazinamide and probenecid on peritoneal urate transport kinetics during continuous ambulatory peritoneal dialysis | journal = Peritoneal Dialysis International | volume = 20 | issue = 1 | pages = 47–52 | year = 2000 | pmid = 10716583 | doi = 10.1177/089686080002000109 | s2cid = 19352495 | doi-access = free }}</ref> and consequently has an ] in the diagnosis of causes of ] and ].<ref name="pmid14694169">{{cite journal | vauthors = Ichida K, Hosoyamada M, Hisatome I, Enomoto A, Hikita M, Endou H, Hosoya T | title = Clinical and molecular analysis of patients with renal hypouricemia in Japan-influence of URAT1 gene on urinary urate excretion | journal = Journal of the American Society of Nephrology | volume = 15 | issue = 1 | pages = 164–173 | date = January 2004 | pmid = 14694169 | doi = 10.1097/01.ASN.0000105320.04395.D0 | doi-access = free }}</ref> It acts on ].<ref name="pmid14694169" />

== Adverse effects ==
The most common (roughly 1%) side effect of pyrazinamide is ]s (arthralgia), but this is not usually so severe that patients need to stop taking it.<ref name="MRC1983">{{cite journal | vauthors = | title = Controlled clinical trial of 4 short-course regimens of chemotherapy (three 6-month and one 8-month) for pulmonary tuberculosis | journal = Tubercle | volume = 64 | issue = 3 | pages = 153–166 | date = September 1983 | pmid = 6356538 | doi = 10.1016/0041-3879(83)90011-9 }}</ref><ref name="BTS">{{cite journal | vauthors = ((British Thoracic Society)) | title = A controlled trial of 6 months' chemotherapy in pulmonary tuberculosis. Final report: results during the 36 months after the end of chemotherapy and beyond. British Thoracic Society | journal = British Journal of Diseases of the Chest | volume = 78 | issue = 4 | pages = 330–336 | date = October 1984 | pmid = 6386028 | doi = 10.1016/0007-0971(84)90165-7 }}</ref> Pyrazinamide can precipitate ] flares by decreasing renal excretion of uric acid.<ref>{{cite journal | title = Treatment of tuberculosis | journal = MMWR. Recommendations and Reports | volume = 52 | issue = RR-11 | pages = 1–77 | date = June 2003 | pmid = 12836625 | url = https://www.cdc.gov/mmwr/PDF/rr/rr5211.pdf | author1 = American Thoracic Society | author2 = CDC | author3 = Infectious Diseases Society of America }}</ref>

The most dangerous side effect of pyrazinamide is ], which is dose-related. The old dose for pyrazinamide was 40–70&nbsp;mg/kg daily and the incidence of drug-induced hepatitis has fallen significantly since the recommended dose has been reduced to 12–30&nbsp;mg/kg daily. In the standard four-drug regimen (isoniazid, rifampicin, pyrazinamide, ]), pyrazinamide is the most common cause of drug-induced hepatitis.<!--
--><ref name="Yee2003">{{cite journal | vauthors = Yee D, Valiquette C, Pelletier M, Parisien I, Rocher I, Menzies D | title = Incidence of serious side effects from first-line antituberculosis drugs among patients treated for active tuberculosis | journal = American Journal of Respiratory and Critical Care Medicine | volume = 167 | issue = 11 | pages = 1472–1477 | date = June 2003 | pmid = 12569078 | doi = 10.1164/rccm.200206-626OC }}</ref> It is not possible to clinically distinguish pyrazinamide-induced hepatitis from hepatitis caused by isoniazid or rifampicin; test dosing is required (this is discussed in detail in ]){{cn|date=August 2022}}

Other ] include ] and ], ], ], ], ], ], ], ], ], rarely ], and ].{{cn|date=August 2022}}

== Pharmacokinetics ==
Pyrazinamide is well absorbed orally. It crosses inflamed meninges and is an essential part of the treatment of ]. It is metabolised by the ] and the metabolic products are excreted by the kidneys.{{cn|date=December 2022}}

Pyrazinamide is routinely used in pregnancy in the UK and the rest of the world; the ] (WHO) recommends its use in pregnancy; and extensive clinical experience shows that it is safe. In the US, pyrazinamide is not used in pregnancy, citing insufficient evidence of safety.<!--
--><ref>{{cite journal | vauthors = Blumberg HM, Burman WJ, Chaisson RE, Daley CL, Etkind SC, Friedman LN, Fujiwara P, Grzemska M, Hopewell PC, Iseman MD, Jasmer RM, Koppaka V, Menzies RI, O'Brien RJ, Reves RR, Reichman LB, Simone PM, Starke JR, Vernon AA | display-authors = 6 | title = American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: treatment of tuberculosis | journal = American Journal of Respiratory and Critical Care Medicine | volume = 167 | issue = 4 | pages = 603–662 | date = February 2003 | pmid = 12588714 | doi = 10.1164/rccm.167.4.603 }}</ref> Pyrazinamide is removed by ], so doses should always be given at the end of a dialysis session.{{medcn|date=January 2020}}

== Mechanism of action ==
Pyrazinamide is a ] that stops the growth of ''M. tuberculosis''.{{cn|date=December 2022}}

Pyrazinamide diffuses into the granuloma of ''M. tuberculosis'', where the tuberculosis enzyme ] converts pyrazinamide to the active form ].<ref name=":0">{{cite journal | vauthors = Whitfield MG, Soeters HM, Warren RM, York T, Sampson SL, Streicher EM, van Helden PD, van Rie A | display-authors = 6 | title = A Global Perspective on Pyrazinamide Resistance: Systematic Review and Meta-Analysis | journal = PLOS ONE | volume = 10 | issue = 7 | pages = e0133869 | date = 28 July 2015 | pmid = 26218737 | pmc = 4517823 | doi = 10.1371/journal.pone.0133869 | doi-access = free | bibcode = 2015PLoSO..1033869W }}</ref> Under acidic conditions of pH 5 to 6, the pyrazinoic acid that slowly leaks out converts to the protonated conjugate acid, which is thought to diffuse easily back into the bacilli and accumulate. The net effect is that more pyrazinoic acid accumulates inside the bacillus at acid pH than at neutral pH.<ref name=":0" /><ref name="pmid12701830">{{cite journal | vauthors = Zhang Y, Mitchison D | title = The curious characteristics of pyrazinamide: a review | journal = The International Journal of Tuberculosis and Lung Disease | volume = 7 | issue = 1 | pages = 6–21 | date = January 2003 | pmid = 12701830 | url = http://openurl.ingenta.com/content/nlm?genre=article&issn=1027-3719&volume=7&issue=1&spage=6&aulast=Zhang }}</ref>

Pyrazinoic acid was thought to inhibit the enzyme ] (FAS) I, which is required by the bacterium to synthesize ]s<ref name="Zimhony2000">{{cite journal | vauthors = Zimhony O, Cox JS, Welch JT, Vilchèze C, Jacobs WR | title = Pyrazinamide inhibits the eukaryotic-like fatty acid synthetase I (FASI) of Mycobacterium tuberculosis | journal = Nature Medicine | volume = 6 | issue = 9 | pages = 1043–1047 | date = September 2000 | pmid = 10973326 | doi = 10.1038/79558 | s2cid = 7409751 }}</ref> although this has been discounted.<ref name="Boschoff2002">{{cite journal | vauthors = Boshoff HI, Mizrahi V, Barry CE | title = Effects of pyrazinamide on fatty acid synthesis by whole mycobacterial cells and purified fatty acid synthase I | journal = Journal of Bacteriology | volume = 184 | issue = 8 | pages = 2167–2172 | date = April 2002 | pmid = 11914348 | pmc = 134955 | doi = 10.1128/JB.184.8.2167-2172.2002 }}</ref><ref name="Zhang">{{cite journal | vauthors = Zhang Y, Shi W, Zhang W, Mitchison D | title = Mechanisms of Pyrazinamide Action and Resistance | journal = Microbiology Spectrum | volume = 2 | issue = 4 | pages = 1–12 | year = 2014 | pmid = 25530919 | pmc = 4268777 | doi = 10.1128/microbiolspec.mgm2-0023-2013 }}</ref> The accumulation of pyrazinoic acid was also suggested to disrupt membrane potential and interfere with energy production, necessary for survival of ''M. tuberculosis'' at an acidic site of infection. However, since an acidic environment is not essential for pyrazinamide susceptibility and pyrazinamide treatment does not lead to intrabacterial acidification nor rapid disruption of membrane potential, this model has also been discounted.<ref>{{cite journal | vauthors = Peterson ND, Rosen BC, Dillon NA, Baughn AD | title = Uncoupling Environmental pH and Intrabacterial Acidification from Pyrazinamide Susceptibility in Mycobacterium tuberculosis | journal = Antimicrobial Agents and Chemotherapy | volume = 59 | issue = 12 | pages = 7320–7326 | date = December 2015 | pmid = 26369957 | pmc = 4649215 | doi = 10.1128/aac.00967-15 }}</ref> Pyrazinoic acid was proposed to bind to the ribosomal protein S1 (RpsA) and inhibit ],<ref name="pmid21835980">{{cite journal | vauthors = Shi W, Zhang X, Jiang X, Yuan H, Lee JS, Barry CE, Wang H, Zhang W, Zhang Y | display-authors = 6 | title = Pyrazinamide inhibits trans-translation in Mycobacterium tuberculosis | journal = Science | volume = 333 | issue = 6049 | pages = 1630–1632 | date = September 2011 | pmid = 21835980 | pmc = 3502614 | doi = 10.1126/science.1208813 | bibcode = 2011Sci...333.1630S }}</ref> but more detailed experiments have shown that it does not have this activity.<ref>{{cite journal | vauthors = Dillon NA, Peterson ND, Feaga HA, Keiler KC, Baughn AD | title = Anti-tubercular Activity of Pyrazinamide is Independent of trans-Translation and RpsA | journal = Scientific Reports | volume = 7 | issue = 1 | pages = 6135 | date = July 2017 | pmid = 28733601 | pmc = 5522395 | doi = 10.1038/s41598-017-06415-5 | bibcode = 2017NatSR...7.6135D }}</ref>

The current hypothesis is that pyrazinoic acid blocks synthesis of ]. Pyrazinoic acid binds weakly to ] ('']''), triggering its degradation.<ref name="Gopal2020">{{cite journal | vauthors = Gopal P, Sarathy JP, Yee M, Ragunathan P, Shin J, Bhushan S, Zhu J, Akopian T, Kandror O, Lim TK, Gengenbacher M, Lin Q, Rubin EJ, Grüber G, Dick T | display-authors = 6 | title = Pyrazinamide triggers degradation of its target aspartate decarboxylase | journal = Nature Communications | volume = 11 | issue = 1 | pages = 1661 | date = April 2020 | pmid = 32245967 | pmc = 7125159 | doi = 10.1038/s41467-020-15516-1 | bibcode = 2020NatCo..11.1661G }}</ref> This is an unusual mechanism of action in that pyrazinamide does not directly block the action of its target, but indirectly triggers its destruction.{{cn|date=August 2022}}

=== Resistance ===
Mutations in the '']'' gene of ''M. tuberculosis'', which encodes a pyrazinamidase and converts pyrazinamide to its active form pyrazinoic acid, are responsible for the majority of pyrazinamide resistance in ''M. tuberculosis'' strains.<ref name="Scorpio1996">{{cite journal | vauthors = Scorpio A, Zhang Y | title = Mutations in pncA, a gene encoding pyrazinamidase/nicotinamidase, cause resistance to the antituberculous drug pyrazinamide in tubercle bacillus | journal = Nature Medicine | volume = 2 | issue = 6 | pages = 662–667 | date = June 1996 | pmid = 8640557 | doi = 10.1038/nm0696-662 | s2cid = 8579133 }}</ref> A few pyrazinamide-resistant strains with mutations in the ''rpsA'' gene have also been identified.<ref name="pmid21835980" /> However, a direct association between these ''rpsA'' mutations and pyrazinamide resistance has not been established. The pyrazinamide-resistant ''M. tuberculosis'' strain DHMH444, which harbors a mutation in the carboxy terminal coding region of ''rpsA'', is fully susceptible to pyrazinoic acid and pyrazinamide resistance of this strain was previously associated with decreased pyrazinamidase activity.<ref>{{cite journal | vauthors = Speirs RJ, Welch JT, Cynamon MH | title = Activity of n-propyl pyrazinoate against pyrazinamide-resistant Mycobacterium tuberculosis: investigations into mechanism of action of and mechanism of resistance to pyrazinamide | journal = Antimicrobial Agents and Chemotherapy | volume = 39 | issue = 6 | pages = 1269–1271 | date = June 1995 | pmid = 7574514 | pmc = 162725 | doi = 10.1128/aac.39.6.1269 }}</ref> Further, this strain was found to be susceptible to pyrazinamide in a mouse model of tuberculosis.<ref>{{cite journal | vauthors = Klemens SP, Sharpe CA, Cynamon MH | title = Activity of pyrazinamide in a murine model against Mycobacterium tuberculosis isolates with various levels of in vitro susceptibility | journal = Antimicrobial Agents and Chemotherapy | volume = 40 | issue = 1 | pages = 14–16 | date = January 1996 | pmid = 8787871 | pmc = 163048 | doi = 10.1128/AAC.40.1.14 }}</ref> Thus, current data indicate that ''rpsA'' mutations are not likely to be associated with pyrazinamide resistance. Currently, three main methods of testing are used for pyrazinamide resistance: 1) phenotypic tests where a tuberculosis strain is grown in the presence of increasing concentrations of pyrazinamide, 2) measuring levels of pyrazinamidase enzyme produced by the tuberculosis strain, or 3) looking for mutations in the '']'' gene of tuberculosis.<ref name=":0" /> Concerns exist that the most widely used method for phenotypic resistance testing may overestimate the number of resistant strains.<ref>{{cite journal | vauthors = Chedore P, Bertucci L, Wolfe J, Sharma M, Jamieson F | title = Potential for erroneous results indicating resistance when using the Bactec MGIT 960 system for testing susceptibility of Mycobacterium tuberculosis to pyrazinamide | journal = Journal of Clinical Microbiology | volume = 48 | issue = 1 | pages = 300–301 | date = January 2010 | pmid = 19923479 | pmc = 2812260 | doi = 10.1128/JCM.01775-09 }}</ref><ref>{{cite journal | vauthors = Piersimoni C, Mustazzolu A, Iacobino A, Giannoni F, Santoro G, Gherardi G, Del Giudice A, Perna R, Fattorini L | display-authors = 6 | title = Pyrazinamide susceptibility testing: proposed new standard with the BACTECTM MGITTM 960 system | journal = The International Journal of Tuberculosis and Lung Disease | volume = 20 | issue = 12 | pages = 1677–1680 | date = December 2016 | pmid = 27931346 | doi = 10.5588/ijtld.16.0360 }}</ref>

Global resistance of tuberculosis to pyrazinamide has been estimated to be in 16% of all cases,{{when|date=January 2020}} and 60% of people with ].<ref name=":0" />

== Abbreviations ==
The abbreviations PZA and Z are standard, and used commonly in the medical literature, although ] discourages the abbreviating of drug names to prevent mistakes.{{medcn|date=January 2020}}

== Presentation ==

Pyrazinamide is a ], and is available in a wide variety of presentations. Pyrazinamide tablets form the bulkiest part of the standard tuberculosis treatment regimen. Pyrazinamide tablets are so large, some people find them impossible to swallow: pyrazinamide syrup is an option.{{cn|date=December 2022}}

Pyrazinamide is also available as part of fixed-dose combinations with other TB drugs such as isoniazid and rifampicin ('']'' is an example).{{cn|date=December 2022}}

== History ==
Pyrazinamide was first discovered and patented in 1936, but not used against tuberculosis until 1952.<ref name="Zhang"/> Its discovery as an antitubercular agent was remarkable since it has no activity against tuberculosis'' ]'', due to not being active at a neutral pH, so would ordinarily not be expected to work '']''.<ref name=":1">{{cite journal | vauthors = Zhang Y, Mitchison D | title = The curious characteristics of pyrazinamide: a review | journal = The International Journal of Tuberculosis and Lung Disease | volume = 7 | issue = 1 | pages = 6–21 | date = January 2003 | pmid = 12701830 }}</ref> However, ] was known to have activity against tuberculosis and pyrazinamide was thought to have a similar effect. Experiments in mice at ] and ] confirmed its ability to kill tuberculosis and it was rapidly used in humans.<ref name=":1" />

== References ==
{{reflist}}

{{Antimycobacterials}}
{{Antigout preparations}}
{{Portal bar | Medicine}}

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