同: PZA

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/04/21 16:08:55」(JST)

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Pyrazinamide is a drug used to treat tuberculosis. The drug is largely bacteriostatic, but can be bacteriocidal on actively replicating tuberculosis bacteria.

It is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system.^[1]

Medical uses

Pyrazinamide is only used in combination with other drugs such as isoniazid and rifampicin in the treatment of Mycobacterium tuberculosis. It is never used on its own. It has no other indicated medical uses. In particular, it is not used to treat other mycobacteria; Mycobacterium bovis and Mycobacterium leprae are innately resistant to pyrazinamide. Pyrazinamide is used in the first two months of treatment to reduce the duration of treatment required.^[2] Regimens not containing pyrazinamide must be taken for nine months or more.

Pyrazinamide in conjunction with rifampin is a preferred treatment for latent tuberculosis.^[3]

Pyrazinamide is a potent antiuricosuric drug^[4] and consequently has an off-label use in the diagnosis of causes of hypouricemia and hyperuricosuria.^[5] It acts on URAT1.^[5]

Adverse effects

The most common (approximately 1%) side effect of pyrazinamide is joint pains (arthralgia), but this is not usually so severe that patients need to stop taking the pyrazinamide.^[6]^[7] Pyrazinamide can precipitate gout flares by decreasing renal excretion of uric acid.^[8]

The most dangerous side effect of pyrazinamide is hepatotoxicity, which is dose related. The old dose for pyrazinamide was 40–70 mg/kg daily and the incidence of drug-induced hepatitis has fallen significantly since the recommended dose has been reduced. In the standard four-drug regimen (isoniazid, rifampicin, pyrazinamide, ethambutol), pyrazinamide is the most common cause of drug-induced hepatitis.^[9] 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 tuberculosis treatment)

Other side effects include nausea and vomiting, anorexia, sideroblastic anemia, skin rash, urticaria, pruritus, dysuria, interstitial nephritis, malaise; rarely porphyria, and fever.

Pharmacokinetics

Pyrazinamide is well absorbed orally. It crosses inflamed meninges and is an essential part of the treatment of tuberculous meningitis. It is metabolised by the liver and the metabolic products are excreted by the kidneys.

Pyrazinamide is routinely used in pregnancy in the UK and the rest of the world; the WHO recommend its use in pregnancy; and there is extensive clinical experience to show that it is safe. In the U.S., pyrazinamide is not used in pregnancy, citing insufficient evidence of safety.^[10] Pyrazinamide is removed by haemodialysis and therefore doses should always be given at the end of a dialysis session.

Mechanism of action

Pyrazinamide is a prodrug that stops the growth of Mycobacterium tuberculosis.

Pyrazinamide diffuses into the granuloma of M. tuberculosis, where the enzyme pyrazinamidase converts pyrazinamide to the active form pyrazinoic acid. Under acidic conditions, 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.^[11]

Pyrazinoic acid was thought to inhibit the enzyme fatty acid synthase (FAS) I, which is required by the bacterium to synthesise fatty acids^[12] although this has been discounted.^[13] It was also suggested that the accumulation of pyrazinoic acid disrupts membrane potential and interferes with energy production, necessary for survival of M. tuberculosis at an acidic site of infection. Further studies reproduced the results of FAS I inhibition as the putative mechanism first in whole cell assay of replicating M. tuberculosis bacilli which have shown that pyrazinoic acid and its ester inhibit the synthesis of fatty acids.^[14] This study was followed by in vitro assay of tuberculous FAS I enzyme that tested the activity with pyrazinamide, pyrazinoic acid and several classes of pyrazinamide analogs. Pyrazinamide and its analogs inhibited the activity of purified FAS I.^[15] Pyrazinoic acid binds to the ribosomal protein S1 (RpsA) and inhibits trans-translation. This may explain the ability of the drug to kill dormant mycobacteria.^[16]

Mutations in the pncA gene, which encodes a pyrazinamidase, is responsible for the appearance of most pyrazinamide resistant M. tuberculosis strains.^[17] A few pyrazinamidase resistant strains with mutations in the rpsA gene have also been identified.^[16]

Abbreviations

The abbreviations PZA and Z are standard, and used commonly in the medical literature, although best practice discourages the abbreviating of drug names to prevent mistakes.

Presentation

Pyrazinamide is a generic drug, 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.

Pyrazinamide is also available as part of fixed-dose combinations with other TB drugs such as isoniazid and rifampicin (Rifater is an example).

References

^ "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014.
^ Hong Kong Chest Service, Medical Research Council (1981). "Controlled trial of four thrice weekly regimens and a daily regimen given for 6 months for pulmonary tuberculosis". Lancet 1 (8213): 171–4. doi:10.1016/S0140-6736(02)95623-0. PMID 6109855.
^ Centers for Disease Control and Prevention (2000). "Targeted tuberculin testing and treatment of latent tuberculosis infection". MMWR 49 (RR–6): 31–32. PMID 10881762.
^ Spaia S, Magoula I, Tsapas G, Vayonas G (2000). "Effect of pyrazinamide and probenecid on peritoneal urate transport kinetics during continuous ambulatory peritoneal dialysis". Perit Dial Int 20 (1): 47–52. PMID 10716583.
^ ^a ^b Ichida K, Hosoyamada M, Hisatome I, Enomoto A, Hikita M, Endou H, Hosoya T (January 2004). "Clinical and molecular analysis of patients with renal hypouricemia in Japan-influence of URAT1 gene on urinary urate excretion". J. Am. Soc. Nephrol. 15 (1): 164–73. doi:10.1097/01.ASN.0000105320.04395.D0. PMID 14694169.
^ East and Central African/Medical Research Council Fifth Collaborative Study (1983). "Controlled clinical trial of 4 short-course regimens of chemotherapy (three 6-month and one 9-month) for pulmonary tuberculosis". Tubercle 64 (3): 153–166. doi:10.1016/0041-3879(83)90011-9. PMID 6356538.
^ British Thoracic Society (1984). "A controlled trial of 6 months chemotherapy in pulmonary tuberculosis, final report: results during the 36 months after the end of chemotherapy and beyond". Br J Dis Chest 78 (4): 330–336. doi:10.1016/0007-0971(84)90165-7. PMID 6386028.
^ American Thoracic Society; CDC; Infectious Diseases Society of America. (Jun 20, 2003). "Treatment of tuberculosis.". MMWR Recomm Rep 52 ((RR-11)): 1–77. PMID 12836625.
^ Yee D, et al. (2003). "Incidence of serious side effects from first-line antituberculosis drugs among patients treated for active tuberculosis". Am J Respir Crit Care Med 167 (11): 1472–7. doi:10.1164/rccm.200206-626OC. PMID 12569078.
^ American Thoracic Society, Centers for Disease Control, Infectious Diseases Society of America (2003). "Treatment of Tuberculosis". Am J Respir Crit Care Med 167: 602–662. doi:10.1164/rccm.167.4.603.
^ Zhang Y, Mitchison D (January 2003). "The curious characteristics of pyrazinamide: a review". Int. J. Tuberc. Lung Dis. 7 (1): 6–21. PMID 12701830.
^ Zimhony O, Cox JS, Welch JT, Vilchèze C, Jacobs WR (2000). "Pyrazinamide inhibits the eukaryotic-like fatty acid synthetase I (FASI) of Mycobacterium tuberculosis" (abstract). Nature Medicine 6 (9): 1043–47. doi:10.1038/79558. PMID 10973326.
^ Boshoff HI, Mizrahi V, Barry CE (2002). "Effects of Pyrazinamide on Fatty Acid Synthesis by Whole Mycobacterial Cells and Purified Fatty Acid Synthase I". Journal of Bacteriology 184 (8): 2167–72. doi:10.1128/JB.184.8.2167-2172.2002. PMC: 134955. PMID 11914348.
^ Zimhony, O; Vilchèze, C; Arai, M; Welch, J. T.; Jacobs Jr, W. R. (2007). "Pyrazinoic acid and its n-propyl ester inhibit fatty acid synthase type I in replicating tubercle bacilli". Antimicrobial Agents and Chemotherapy 51 (2): 752–4. doi:10.1128/AAC.01369-06. PMC: 1797748. PMID 17101678.
^ Ngo, S. C.; Zimhony, O; Chung, W. J.; Sayahi, H; Jacobs Jr, W. R.; Welch, J. T. (2007). "Inhibition of Isolated Mycobacterium tuberculosis Fatty Acid Synthase I by Pyrazinamide Analogs". Antimicrobial Agents and Chemotherapy 51 (7): 2430–2435. doi:10.1128/AAC.01458-06. PMC: 1913273. PMID 17485499.
^ ^a ^b Shi W, Zhang X, Jiang X, Yuan H, Lee JS, Barry CE, et al. (2011). "Pyrazinamide inhibits trans-translation in Mycobacterium tuberculosis". Science 333 (6049): 1630–1632. doi:10.1126/science.1208813. PMC: 3502614. PMID 21835980.
^ Scorpio A, Zhang Y (1996). "Mutations in pncA, a gene encoding pyrazinamidase/nicotinamidase, cause resistance to the antituberculous drug pyrazinamide in tubercle bacillus". Nature Medicine 2 (6): 662–7. doi:10.1038/nm0696-662. PMID 8640557.

UpToDate Contents

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1. ピラジンアミド：概要 pyrazinamide an overview
2. 非HIV感染患者における肺結核の治療 treatment of pulmonary tuberculosis in hiv uninfected patients
3. 薬剤耐性結核の診断、治療、および予防 diagnosis treatment and prevention of drug resistant tuberculosis
4. 薬剤耐性結核の疫学および分子メカニズム epidemiology and molecular mechanisms of drug resistant tuberculosis
5. Treatment of pulmonary tuberculosis in HIV-infected adults

English Journal

Characterisation of pyrazinamide-resistant Mycobacterium tuberculosis strains isolated in Poland and Germany.

Napiórkowska A1, Rüsch-Gerdes S2, Hillemann D2, Richter E2, Augustynowicz-Kopeć E1.Author information 1Department of Microbiology, National Tuberculosis and Lung Diseases Research Institute, Warsaw, Poland.2The National Reference Centre for Mycobacteria, Forschungszentrim Borstel, Germany.AbstractBACKGROUND: Pyrazinamide (PZA) is an important first-line anti-tuberculosis drug that is generally administered with isoniazid, rifampicin, ethambutol and streptomycin.
The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.Int J Tuberc Lung Dis.2014 Apr;18(4):454-60. doi: 10.5588/ijtld.13.0457.
BACKGROUND: Pyrazinamide (PZA) is an important first-line anti-tuberculosis drug that is generally administered with isoniazid, rifampicin, ethambutol and streptomycin.OBJECTIVE: To analyse the correlation between phenotypic resistance to PZA and genotype to find out whether the great diversity in p
PMID 24670702

Highly sensitive and selective determination of pyrazinamide at poly-L-methionine/reduced graphene oxide modified electrode by differential pulse voltammetry in human blood plasma and urine samples.

Cheemalapati S1, Devadas B1, Chen SM2.Author information 1Electroanalysis and Bioelectrochemistry Lab, Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, No. 1, Section 3, Chung-Hsiao East Road, Taipei 106, Taiwan, ROC.2Electroanalysis and Bioelectrochemistry Lab, Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, No. 1, Section 3, Chung-Hsiao East Road, Taipei 106, Taiwan, ROC. Electronic address: smchen78@ms15.hinet.net.AbstractIn this current study we used electrochemically active film which contains poly-L-methionine (PMET) and electrochemically reduced graphene oxide (ERGO) on glassy carbon electrode (GCE) for pyrazinamide (PZM) detection. The electrocatalytic response of analyte at PMET/ERGO/GCE film was measured using both cyclic voltammetry (CV) and differential pulse voltammetry (DPV). In addition, electrochemical impedance studies revealed that the smaller R(ct) value observed at PMET/ERGO film modified GCE which authenticates its good conductivity and faster electron transfer rate. The prepared PMET/ERGO/GCE film exhibits excellent DPV response towards PZM and the reduction peak current increased linearly with respect to PZM concentration in the linear range between 0.4 μM to 1129 μM with a sensitivity of 0.266 μA μM(-1) cm(-2). Real sample studies were carried out in human blood plasma and urine samples, which offered good recovery and revealed the promising practicality of the sensor for PZM detection. The proposed sensor displayed a good selectivity, repeatability, sensitivity with appreciable consistency and good reproducibility. In addition, the proposed electrochemical sensor showed good results towards the commercial pharmaceutical PZM samples.
Journal of colloid and interface science.J Colloid Interface Sci.2014 Mar 15;418:132-9. doi: 10.1016/j.jcis.2013.11.084. Epub 2013 Dec 7.
In this current study we used electrochemically active film which contains poly-L-methionine (PMET) and electrochemically reduced graphene oxide (ERGO) on glassy carbon electrode (GCE) for pyrazinamide (PZM) detection. The electrocatalytic response of analyte at PMET/ERGO/GCE film was measured using
PMID 24461828

Salicylanilide pyrazinoates inhibit in vitro multidrug-resistant Mycobacterium tuberculosis strains, atypical mycobacteria and isocitrate lyase.

Krátký M1, Vinšová J2, Novotná E3, Stolaříková J4.Author information 1Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Charles University in Prague, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic. Electronic address: martin.kratky@faf.cuni.cz.2Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Charles University in Prague, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic. Electronic address: jarmila.vinsova@faf.cuni.cz.3Department of Biochemical Sciences, Faculty of Pharmacy, Charles University in Prague, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic. Electronic address: eva.novotna@faf.cuni.cz.4Laboratory for Mycobacterial Diagnostics and Tuberculosis, Regional Institute of Public Health in Ostrava, Partyzánské náměstí 7, 702 00 Ostrava, Czech Republic. Electronic address: jirina.stolarikova@zu.cz.AbstractThe development of antimicrobial agents represents an up-to-date topic. This study investigated in vitro antimycobacterial activity, mycobacterial isocitrate lyase inhibition and cytotoxicity of salicylanilide pyrazinoates. They may be considered being mutual prodrugs of both antimycobacterial active salicylanilides and pyrazinoic acid (POA), an active metabolite of pyrazinamide, in which these esters are likely hydrolysed without presence of pyrazinamidase/nicotinamidase. Minimum inhibitory concentrations (MICs) of the esters were within the range 0.5-8 μmol/l for Mycobacterium tuberculosis and 1-32 μmol/l for nontuberculous mycobacteria (Mycobacterium avium, Mycobacterium kansasii). All esters showed a weak inhibition (8-17%) of isocitrate lyase at the concentration of 10 μmol/l. The most active pyrazinoates showed MICs for multidrug-resistant tuberculosis strains in the range of 0.125-2 μmol/l and no cross-resistance with clinically used drugs, thus being the most in vitro efficacious salicylanilide esters with 4-chloro-2-{[4-(trifluoromethyl)phenyl]carbamoyl}phenyl pyrazine-2-carboxylate superiority (MICs⩽0.25 μmol/l). This promising activity is likely due to an additive or synergistic effect of released POA and salicylanilides. Selectivity indexes for the most active salicylanilide pyrazinoates ranged up to 64, making some derivatives being attractive candidates for the next research; 4-bromo-2-{[4-(trifluoromethyl)phenyl]carbamoyl}phenyl pyrazine-2-carboxylate showed the most convenient toxicity profile.
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.Eur J Pharm Sci.2014 Mar 12;53:1-9. doi: 10.1016/j.ejps.2013.12.001. Epub 2013 Dec 10.
The development of antimicrobial agents represents an up-to-date topic. This study investigated in vitro antimycobacterial activity, mycobacterial isocitrate lyase inhibition and cytotoxicity of salicylanilide pyrazinoates. They may be considered being mutual prodrugs of both antimycobacterial activ
PMID 24333643

Japanese Journal

Primary Gastric Tuberculosis Presenting as Non-Healing Ulcer and Mimicking Crohns Disease

Ishii Naoki,Furukawa Keiichi,Itoh Toshiyuki,Fujita Yoshiyuki
Internal Medicine 50(5), 439-442, 2011
… The differential diagnosis included gastric tuberculosis, Crohns disease, and sarcoidosis and empiric antituberculous therapy consisting of isoniazid, rifampicin, ethambutol, and pyrazinamide was initiated. …
NAID 130000649855

Simultaneous Determination of Isoniazid, Pyrazinamide, Rifampicin and Acetylisoniazid in Human Plasma by High-Performance Liquid Chromatography

ZHOU Zhifeng,CHEN Lingyun,LIU Peng,SHEN Mei,ZOU Fei
Analytical sciences : the international journal of the Japan Society for Analytical Chemistry 26(11), 1133-1138, 2010-11-10
NAID 10027315955

Identification of Mycobacterium tuberculosis clinical isolates in Bangladesh by a species distinguishable multiplex PCR

Nakajima Chie,Rahim Zeaur,Fukushima Yukari,Sugawara Isamu,van der Zanden Adri G. M.,Tamaru Aki,Suzuki Yasuhiko
BMC Infectious Diseases 10, 118, 2010-05-15
… bovis is naturally resistant to a first line anti-tuberculosis (TB) drug, pyrazinamide, while most of the other MTC members are susceptible to this antimicrobial agent. … This result suggested the general TB treatment regimen including pyrazinamide to be the first choice in Bangladesh. …
NAID 120002232150

Related Pictures

★リンクテーブル★

リンク元	「ピラジナミド」「PZA」

「ピラジナミド」

Pyrazinamide
Systematic (IUPAC) name
	pyrazine-2-carboxamide
Clinical data
Trade names	Rifater
AHFS/Drugs.com	monograph
MedlinePlus	a682402
Pregnancy; category	C;
Routes of; administration	Oral
Legal status
Legal status	?;
Pharmacokinetic data
Bioavailability	>90%
Metabolism	Hepatic
Biological half-life	9 to 10 hours
Excretion	Renal
Identifiers
CAS Number	98-96-4
ATC code	J04AK01 (WHO)
PubChem	CID 1046
IUPHAR/BPS	7287
DrugBank	DB00339
ChemSpider	1017
UNII	2KNI5N06TI
KEGG	D00144
ChEBI	CHEBI:45285
ChEMBL	CHEMBL614
NIAID ChemDB	007697
Chemical data
Formula	C5H5N3O
Molar mass	123.113 g/mol
	SMILES O=C(N)c1nccnc1 ;
	InChI InChI=1S/C5H5N3O/c6-5(9)4-3-7-1-2-8-4/h1-3H,(H2,6,9) ; Key:IPEHBUMCGVEMRF-UHFFFAOYSA-N ;
(verify)

　　[★]

英: pyrazinamide PZA
ラ: pyrazinamidum
同: ピラジンカルボキサミド pyrazinecarboxamide
商: ピラマイド？, Pyramide
関: 抗結核薬、結核

副作用：(多い)肝障害、高尿酸血症、関節痛
厚労省が告示した治療法(結核#2009年に厚生労働省告示)ではA法で使用されている。おそらく副作用などでピラジナミドが使用できない場合にはB法を用いると思われる。

参考

1. [charged] ピラジンアミド：概要 - uptodate [1]

「PZA」

　　[★] ピラジナミド pyrazinamide

同: pyrazinamide

[1] "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014.

[MRC-2] Hong Kong Chest Service, Medical Research Council (1981). "Controlled trial of four thrice weekly regimens and a daily regimen given for 6 months for pulmonary tuberculosis". Lancet 1 (8213): 171–4. doi:10.1016/S0140-6736(02)95623-0. PMID 6109855.

[3] Centers for Disease Control and Prevention (2000). "Targeted tuberculin testing and treatment of latent tuberculosis infection". MMWR 49 (RR–6): 31–32. PMID 10881762.

[pmid10716583-4] Spaia S, Magoula I, Tsapas G, Vayonas G (2000). "Effect of pyrazinamide and probenecid on peritoneal urate transport kinetics during continuous ambulatory peritoneal dialysis". Perit Dial Int 20 (1): 47–52. PMID 10716583.

[pmid14694169-5] Ichida K, Hosoyamada M, Hisatome I, Enomoto A, Hikita M, Endou H, Hosoya T (January 2004). "Clinical and molecular analysis of patients with renal hypouricemia in Japan-influence of URAT1 gene on urinary urate excretion". J. Am. Soc. Nephrol. 15 (1): 164–73. doi:10.1097/01.ASN.0000105320.04395.D0. PMID 14694169.

[MRC1983-6] East and Central African/Medical Research Council Fifth Collaborative Study (1983). "Controlled clinical trial of 4 short-course regimens of chemotherapy (three 6-month and one 9-month) for pulmonary tuberculosis". Tubercle 64 (3): 153–166. doi:10.1016/0041-3879(83)90011-9. PMID 6356538.

[BTS-7] British Thoracic Society (1984). "A controlled trial of 6 months chemotherapy in pulmonary tuberculosis, final report: results during the 36 months after the end of chemotherapy and beyond". Br J Dis Chest 78 (4): 330–336. doi:10.1016/0007-0971(84)90165-7. PMID 6386028.

[8] American Thoracic Society; CDC; Infectious Diseases Society of America. (Jun 20, 2003). "Treatment of tuberculosis.". MMWR Recomm Rep 52 ((RR-11)): 1–77. PMID 12836625.

[Yee2003-9] Yee D, et al. (2003). "Incidence of serious side effects from first-line antituberculosis drugs among patients treated for active tuberculosis". Am J Respir Crit Care Med 167 (11): 1472–7. doi:10.1164/rccm.200206-626OC. PMID 12569078.

[-10] American Thoracic Society, Centers for Disease Control, Infectious Diseases Society of America (2003). "Treatment of Tuberculosis". Am J Respir Crit Care Med 167: 602–662. doi:10.1164/rccm.167.4.603.

[pmid12701830-11] Zhang Y, Mitchison D (January 2003). "The curious characteristics of pyrazinamide: a review". Int. J. Tuberc. Lung Dis. 7 (1): 6–21. PMID 12701830.

[Zimhony2000-12] Zimhony O, Cox JS, Welch JT, Vilchèze C, Jacobs WR (2000). "Pyrazinamide inhibits the eukaryotic-like fatty acid synthetase I (FASI) of Mycobacterium tuberculosis" (abstract). Nature Medicine 6 (9): 1043–47. doi:10.1038/79558. PMID 10973326.

[Boschoff2002-13] Boshoff HI, Mizrahi V, Barry CE (2002). "Effects of Pyrazinamide on Fatty Acid Synthesis by Whole Mycobacterial Cells and Purified Fatty Acid Synthase I". Journal of Bacteriology 184 (8): 2167–72. doi:10.1128/JB.184.8.2167-2172.2002. PMC: 134955. PMID 11914348.

[14] Zimhony, O; Vilchèze, C; Arai, M; Welch, J. T.; Jacobs Jr, W. R. (2007). "Pyrazinoic acid and its n-propyl ester inhibit fatty acid synthase type I in replicating tubercle bacilli". Antimicrobial Agents and Chemotherapy 51 (2): 752–4. doi:10.1128/AAC.01369-06. PMC: 1797748. PMID 17101678.

[15] Ngo, S. C.; Zimhony, O; Chung, W. J.; Sayahi, H; Jacobs Jr, W. R.; Welch, J. T. (2007). "Inhibition of Isolated Mycobacterium tuberculosis Fatty Acid Synthase I by Pyrazinamide Analogs". Antimicrobial Agents and Chemotherapy 51 (7): 2430–2435. doi:10.1128/AAC.01458-06. PMC: 1913273. PMID 17485499.

[pmid21835980-16] Shi W, Zhang X, Jiang X, Yuan H, Lee JS, Barry CE, et al. (2011). "Pyrazinamide inhibits trans-translation in Mycobacterium tuberculosis". Science 333 (6049): 1630–1632. doi:10.1126/science.1208813. PMC: 3502614. PMID 21835980.

[Scorpio1996-17] Scorpio A, Zhang Y (1996). "Mutations in pncA, a gene encoding pyrazinamidase/nicotinamidase, cause resistance to the antituberculous drug pyrazinamide in tubercle bacillus". Nature Medicine 2 (6): 662–7. doi:10.1038/nm0696-662. PMID 8640557.

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案内

pyrazinamide