Pyrazinamide - DrugBank

ID Pharmacology Interactions References Trials Economics Properties Spectra Taxonomy

Targets (1)Enzymes (4)

Targets (1)Enzymes (4)Biointeractions (4)

Identification

Name

Pyrazinamide

Accession Number

DB00339 (APRD01206)

Type

Small Molecule

Groups

Approved

Description

A pyrazine that is used therapeutically as an antitubercular agent.

Structure

MOL SDF 3D-SDF PDB SMILES InChI View 3D Structure

Synonyms

2-carbamylpyrazine

2-pyrazinecarboxamide

Aldinamide

Pirazinamida

Pirazinamide

Pyrazinamid

Pyrazinamida

Pyrazinamide

Pyrazinamidum

Pyrazine carboxamide

pyrazine-2-carboxamide

Pyrazineamide

Pyrazinecarboxamide

Pyrazinoic acid amide

Pyrizinamide

External IDs

D-50 / MK-56 / NSC-14911 / PZA / Z

Product Ingredients

Not Available

Approved Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Pdp-pyrazinamide	Tablet	500 mg	Oral	Pendopharm Division Of De Pharmascience Inc	1984-12-31	Not applicable	Canada
Tebrazid Tab 500mg	Tablet	500 mg	Oral	Valeant Canada Lp Valeant Canada S.E.C.	1973-12-31	Not applicable	Canada

Approved Generic Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Pyrazinamide	Tablet	500 mg/1	Oral	Remedy Repack	2013-08-21	2017-01-13	US
Pyrazinamide	Tablet	500 mg/1	Oral	A S Medication Solutions	1971-06-03	2017-06-20	US
Pyrazinamide	Tablet	500 mg/1	Oral	A S Medication Solutions	1995-04-01	2017-06-20	US
Pyrazinamide	Tablet	500 mg/1	Oral	Clinical Solutions Wholsesale	1971-06-03	2017-06-20	US
Pyrazinamide	Tablet	500 mg/1	Oral	Mikart, Inc.	1992-06-30	2017-01-11	US
Pyrazinamide	Tablet	500 mg/1	Oral	DAVA Pharmaceuticals, Inc.	1971-06-03	Not applicable	US
Pyrazinamide	Tablet	500 mg/1	Oral	A S Medication Solutions	1995-04-01	2017-06-20	US
Pyrazinamide	Tablet	500 mg/1	Oral	Remedy Repack	2011-06-30	2016-10-21	US
Pyrazinamide	Tablet	500 mg/1	Oral	Remedy Repack	2008-05-21	Not applicable	US
Pyrazinamide	Tablet	500 mg/1	Oral	Amerincan Health Packaging	2015-09-01	Not applicable	US
Pyrazinamide	Tablet	500 mg/1	Oral	Department Of State Health Services, Pharmacy Branch	1995-04-01	Not applicable	US
Pyrazinamide	Tablet	500 mg/1	Oral	Remedy Repack	2016-12-27	Not applicable	US
Pyrazinamide	Tablet	500 mg/1	Oral	Remedy Repack	2013-02-26	2016-10-13	US
Pyrazinamide	Tablet	500 mg/1	Oral	Versa Pharm Incorporated	1995-04-01	Not applicable	US

Approved Over the Counter Products

Not Available

Unapproved/Other Products

Not Available

International Brands

Name	Company
Piraldina	Bracco
Prazina	Armoxindo
Pyrafat	Riemser
Pyrazide	Sanofi-Aventis
Tebrazid	Valeant
Tisamid	Orion

Brand mixtures

Name	Labeller	Ingredients
Rifater	Remedy Repack	Isoniazid Pyrazinamide Rifampicin

Categories

UNII

2KNI5N06TI

CAS number

98-96-4

Weight

Average: 123.1127
Monoisotopic: 123.043261797

Chemical Formula

C₅H₅N₃O

InChI Key

IPEHBUMCGVEMRF-UHFFFAOYSA-N

InChI

InChI=1S/C5H5N3O/c6-5(9)4-3-7-1-2-8-4/h1-3H,(H2,6,9)

IUPAC Name

pyrazine-2-carboxamide

SMILES

NC(=O)C1=NC=CN=C1

Pharmacology

Indication

For the initial treatment of active tuberculosis in adults and children when combined with other antituberculous agents.

Structured Indications

Active Tuberculosis

Pharmacodynamics

Pyrazinamide kills or stops the growth of certain bacteria that cause tuberculosis (TB). It is used with other drugs to treat tuberculosis. It is a highly specific agent and is active only against Mycobacterium tuberculosis. In vitro and in vivo, the drug is active only at a slightly acid pH. Pyrazinamie gets activated to Pyrazinoic acid in the bacilli where it interferes with fatty acid synthase FAS I. This interferes with the bacteriums ability to synthesize new fatty acids, required for growth and replication.

Mechanism of action

Pyrazinamide diffuses into 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. Pyrazinoic acid was thought to inhibit the enzyme fatty acid synthase (FAS) I, which is required by the bacterium to synthesise fatty acids. However, this theory was thought to have been discounted (PMID: 11914348). However, 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 (PMID: 17101678). 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 (PMID: 17485499).

It has also been 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.

Pyrazinoic acid has also been shown to bind to the ribosomal protein S1 (RpsA) and inhibit trans-translation. This may explain the ability of the drug to kill dormant mycobacteria (PMID: 21835980).

Target	Kind	Pharmacological action	Actions	Organism	UniProt ID
Fatty acid synthetase I (FASI)	Protein	yes	inhibitor	Mycobacterium tuberculosis	not applicable	details

Absorption

Rapidly and well absorbed from the gastrointestinal tract.

Volume of distribution

Not Available

Protein binding

~10% (bound to plasma proteins)

Metabolism

Hepatic.

Substrate	Enzymes	Product
Pyrazinamide	Aldehyde oxidase	5-hydroxypyrazinamide	Details

Route of elimination

Approximately 70% of an oral dose is excreted in the urine, mainly by glomerular filtration within 24 hours

Half life

9-10 hours (normal conditions)

Clearance

Not Available

Toxicity

Side effects include liver injury, arthralgias, anorexia, nausea and vomiting, dysuria,malaise and fever, sideroblastic anemia, adverse effects on the blood clotting mechanism or vascular integrity, and hypersensitivity reactions such as urticaria, pruritis and skin rashes.

Affected organisms

Mycobacterium tuberculosis

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

Drug	Interaction	Drug group
Abiraterone	The serum concentration of Pyrazinamide can be increased when it is combined with Abiraterone.	Approved
Amiodarone	The metabolism of Pyrazinamide can be decreased when combined with Amiodarone.	Approved, Investigational
Aprepitant	The serum concentration of Pyrazinamide can be increased when it is combined with Aprepitant.	Approved, Investigational
Atazanavir	The metabolism of Pyrazinamide can be decreased when combined with Atazanavir.	Approved, Investigational
Atomoxetine	The metabolism of Pyrazinamide can be decreased when combined with Atomoxetine.	Approved
Azithromycin	The metabolism of Pyrazinamide can be decreased when combined with Azithromycin.	Approved
BCG vaccine	The therapeutic efficacy of Bcg can be decreased when used in combination with Pyrazinamide.	Investigational
Bexarotene	The serum concentration of Pyrazinamide can be decreased when it is combined with Bexarotene.	Approved, Investigational
Boceprevir	The metabolism of Pyrazinamide can be decreased when combined with Boceprevir.	Withdrawn
Bortezomib	The metabolism of Pyrazinamide can be decreased when combined with Bortezomib.	Approved, Investigational
Bosentan	The serum concentration of Pyrazinamide can be decreased when it is combined with Bosentan.	Approved, Investigational
Caffeine	The metabolism of Pyrazinamide can be decreased when combined with Caffeine.	Approved
Carbamazepine	The metabolism of Pyrazinamide can be increased when combined with Carbamazepine.	Approved, Investigational
Ceritinib	The serum concentration of Pyrazinamide can be increased when it is combined with Ceritinib.	Approved
Citalopram	The metabolism of Pyrazinamide can be decreased when combined with Citalopram.	Approved
Clarithromycin	The metabolism of Pyrazinamide can be decreased when combined with Clarithromycin.	Approved
Clemastine	The metabolism of Pyrazinamide can be decreased when combined with Clemastine.	Approved
Clotrimazole	The metabolism of Pyrazinamide can be decreased when combined with Clotrimazole.	Approved, Vet Approved
Cobicistat	The metabolism of Pyrazinamide can be decreased when combined with Cobicistat.	Approved
Conivaptan	The serum concentration of Pyrazinamide can be increased when it is combined with Conivaptan.	Approved, Investigational
Crizotinib	The metabolism of Pyrazinamide can be decreased when combined with Crizotinib.	Approved
Cyclosporine	The serum concentration of Cyclosporine can be increased when it is combined with Pyrazinamide.	Approved, Investigational, Vet Approved
Cyclosporine	The metabolism of Pyrazinamide can be decreased when combined with Cyclosporine.	Approved, Investigational, Vet Approved
Cyproterone acetate	The serum concentration of Pyrazinamide can be decreased when it is combined with Cyproterone acetate.	Approved, Investigational
Dabrafenib	The serum concentration of Pyrazinamide can be decreased when it is combined with Dabrafenib.	Approved
Darunavir	The metabolism of Pyrazinamide can be decreased when combined with Darunavir.	Approved
Dasatinib	The serum concentration of Pyrazinamide can be increased when it is combined with Dasatinib.	Approved, Investigational
Deferasirox	The serum concentration of Pyrazinamide can be decreased when it is combined with Deferasirox.	Approved, Investigational
Delavirdine	The metabolism of Pyrazinamide can be decreased when combined with Delavirdine.	Approved
Dexamethasone	The serum concentration of Pyrazinamide can be decreased when it is combined with Dexamethasone.	Approved, Investigational, Vet Approved
Dihydroergotamine	The metabolism of Pyrazinamide can be decreased when combined with Dihydroergotamine.	Approved
Diltiazem	The metabolism of Pyrazinamide can be decreased when combined with Diltiazem.	Approved
Doxycycline	The metabolism of Pyrazinamide can be decreased when combined with Doxycycline.	Approved, Investigational, Vet Approved
Dronedarone	The metabolism of Pyrazinamide can be decreased when combined with Dronedarone.	Approved
Efavirenz	The serum concentration of Pyrazinamide can be decreased when it is combined with Efavirenz.	Approved, Investigational
Enzalutamide	The serum concentration of Pyrazinamide can be decreased when it is combined with Enzalutamide.	Approved
Erythromycin	The metabolism of Pyrazinamide can be decreased when combined with Erythromycin.	Approved, Vet Approved
Eslicarbazepine acetate	The serum concentration of Pyrazinamide can be decreased when it is combined with Eslicarbazepine acetate.	Approved
Etravirine	The serum concentration of Pyrazinamide can be decreased when it is combined with Etravirine.	Approved
Fluconazole	The metabolism of Pyrazinamide can be decreased when combined with Fluconazole.	Approved
Fluvoxamine	The metabolism of Pyrazinamide can be decreased when combined with Fluvoxamine.	Approved, Investigational
Fosamprenavir	The metabolism of Pyrazinamide can be decreased when combined with Fosamprenavir.	Approved
Fosaprepitant	The serum concentration of Pyrazinamide can be increased when it is combined with Fosaprepitant.	Approved
Fosphenytoin	The metabolism of Pyrazinamide can be increased when combined with Fosphenytoin.	Approved
Fusidic Acid	The serum concentration of Pyrazinamide can be increased when it is combined with Fusidic Acid.	Approved
Idelalisib	The serum concentration of Pyrazinamide can be increased when it is combined with Idelalisib.	Approved
Imatinib	The metabolism of Pyrazinamide can be decreased when combined with Imatinib.	Approved
Indinavir	The metabolism of Pyrazinamide can be decreased when combined with Indinavir.	Approved
Isavuconazonium	The metabolism of Pyrazinamide can be decreased when combined with Isavuconazonium.	Approved, Investigational
Isradipine	The metabolism of Pyrazinamide can be decreased when combined with Isradipine.	Approved
Itraconazole	The metabolism of Pyrazinamide can be decreased when combined with Itraconazole.	Approved, Investigational
Ivacaftor	The serum concentration of Pyrazinamide can be increased when it is combined with Ivacaftor.	Approved
Ketoconazole	The metabolism of Pyrazinamide can be decreased when combined with Ketoconazole.	Approved, Investigational
Lidocaine	The metabolism of Pyrazinamide can be decreased when combined with Lidocaine.	Approved, Vet Approved
Lopinavir	The metabolism of Pyrazinamide can be decreased when combined with Lopinavir.	Approved
Lovastatin	The metabolism of Pyrazinamide can be decreased when combined with Lovastatin.	Approved, Investigational
Luliconazole	The serum concentration of Pyrazinamide can be increased when it is combined with Luliconazole.	Approved
Lumacaftor	The metabolism of Pyrazinamide can be increased when combined with Lumacaftor.	Approved
Mexiletine	The metabolism of Pyrazinamide can be decreased when combined with Mexiletine.	Approved
Mifepristone	The serum concentration of Pyrazinamide can be increased when it is combined with Mifepristone.	Approved, Investigational
Mitotane	The serum concentration of Pyrazinamide can be decreased when it is combined with Mitotane.	Approved
Modafinil	The serum concentration of Pyrazinamide can be decreased when it is combined with Modafinil.	Approved, Investigational
Nafcillin	The serum concentration of Pyrazinamide can be decreased when it is combined with Nafcillin.	Approved
Nefazodone	The metabolism of Pyrazinamide can be decreased when combined with Nefazodone.	Approved, Withdrawn
Nelfinavir	The metabolism of Pyrazinamide can be decreased when combined with Nelfinavir.	Approved
Netupitant	The serum concentration of Pyrazinamide can be increased when it is combined with Netupitant.	Approved
Nevirapine	The metabolism of Pyrazinamide can be increased when combined with Nevirapine.	Approved
Nilotinib	The metabolism of Pyrazinamide can be decreased when combined with Nilotinib.	Approved, Investigational
Olaparib	The metabolism of Pyrazinamide can be decreased when combined with Olaparib.	Approved
Osimertinib	The serum concentration of Pyrazinamide can be increased when it is combined with Osimertinib.	Approved
Palbociclib	The serum concentration of Pyrazinamide can be increased when it is combined with Palbociclib.	Approved
Peginterferon alfa-2b	The serum concentration of Pyrazinamide can be increased when it is combined with Peginterferon alfa-2b.	Approved
Pentobarbital	The metabolism of Pyrazinamide can be increased when combined with Pentobarbital.	Approved, Vet Approved
Phenobarbital	The metabolism of Pyrazinamide can be increased when combined with Phenobarbital.	Approved
Phenytoin	The metabolism of Pyrazinamide can be increased when combined with Phenytoin.	Approved, Vet Approved
Picosulfuric acid	The therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Pyrazinamide.	Approved
Posaconazole	The metabolism of Pyrazinamide can be decreased when combined with Posaconazole.	Approved, Investigational, Vet Approved
Primidone	The metabolism of Pyrazinamide can be increased when combined with Primidone.	Approved, Vet Approved
Ranolazine	The metabolism of Pyrazinamide can be decreased when combined with Ranolazine.	Approved, Investigational
Rifabutin	The metabolism of Pyrazinamide can be increased when combined with Rifabutin.	Approved
Rifampicin	Pyrazinamide may increase the hepatotoxic activities of Rifampicin.	Approved
Rifapentine	The metabolism of Pyrazinamide can be increased when combined with Rifapentine.	Approved
Ritonavir	The metabolism of Pyrazinamide can be decreased when combined with Ritonavir.	Approved, Investigational
Ropinirole	The metabolism of Pyrazinamide can be decreased when combined with Ropinirole.	Approved, Investigational
Saquinavir	The metabolism of Pyrazinamide can be decreased when combined with Saquinavir.	Approved, Investigational
Sildenafil	The metabolism of Pyrazinamide can be decreased when combined with Sildenafil.	Approved, Investigational
Siltuximab	The serum concentration of Pyrazinamide can be decreased when it is combined with Siltuximab.	Approved
Simeprevir	The serum concentration of Pyrazinamide can be increased when it is combined with Simeprevir.	Approved
St. John's Wort	The serum concentration of Pyrazinamide can be decreased when it is combined with St. John's Wort.	Nutraceutical
Stiripentol	The serum concentration of Pyrazinamide can be increased when it is combined with Stiripentol.	Approved
Sulfisoxazole	The metabolism of Pyrazinamide can be decreased when combined with Sulfisoxazole.	Approved, Vet Approved
Telaprevir	The metabolism of Pyrazinamide can be decreased when combined with Telaprevir.	Withdrawn
Telithromycin	The metabolism of Pyrazinamide can be decreased when combined with Telithromycin.	Approved
Tenofovir disoproxil	The metabolism of Pyrazinamide can be decreased when combined with Tenofovir.	Approved, Investigational
Teriflunomide	The serum concentration of Pyrazinamide can be decreased when it is combined with Teriflunomide.	Approved
Theophylline	The metabolism of Pyrazinamide can be decreased when combined with Theophylline.	Approved
Ticlopidine	The metabolism of Pyrazinamide can be decreased when combined with Ticlopidine.	Approved
Tocilizumab	The serum concentration of Pyrazinamide can be decreased when it is combined with Tocilizumab.	Approved
Vemurafenib	The serum concentration of Pyrazinamide can be increased when it is combined with Vemurafenib.	Approved
Venlafaxine	The metabolism of Pyrazinamide can be decreased when combined with Venlafaxine.	Approved
Verapamil	The metabolism of Pyrazinamide can be decreased when combined with Verapamil.	Approved
Voriconazole	The metabolism of Pyrazinamide can be decreased when combined with Voriconazole.	Approved, Investigational
Ziprasidone	The metabolism of Pyrazinamide can be decreased when combined with Ziprasidone.	Approved

Food Interactions

Take without regard to meals.

References

Synthesis Reference

Not Available

General References

Authors unspecified: Controlled trial of four thrice-weekly regimens and a daily regimen all given for 6 months for pulmonary tuberculosis. Lancet. 1981 Jan 24;1(8213):171-4. [PubMed:6109855 ]
Authors unspecified: Controlled clinical trial of 4 short-couse regimens of chemotherapy (three 6-month and one 8-month) for pulmonary tuberculosis. Tubercle. 1983 Sep;64(3):153-66. [PubMed:6356538 ]
Authors unspecified: 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. Br J Dis Chest. 1984 Oct;78(4):330-6. [PubMed:6386028 ]
Yee D, Valiquette C, Pelletier M, Parisien I, Rocher I, Menzies D: Incidence of serious side effects from first-line antituberculosis drugs among patients treated for active tuberculosis. Am J Respir Crit Care Med. 2003 Jun 1;167(11):1472-7. Epub 2003 Jan 31. [PubMed:12569078 ]
Boshoff HI, Mizrahi V, Barry CE 3rd: Effects of pyrazinamide on fatty acid synthesis by whole mycobacterial cells and purified fatty acid synthase I. J Bacteriol. 2002 Apr;184(8):2167-72. [PubMed:11914348 ]
Zimhony O, Vilcheze C, Arai M, Welch JT, Jacobs WR Jr: Pyrazinoic acid and its n-propyl ester inhibit fatty acid synthase type I in replicating tubercle bacilli. Antimicrob Agents Chemother. 2007 Feb;51(2):752-4. Epub 2006 Nov 13. [PubMed:17101678 ]
Ngo SC, Zimhony O, Chung WJ, Sayahi H, Jacobs WR Jr, Welch JT: Inhibition of isolated Mycobacterium tuberculosis fatty acid synthase I by pyrazinamide analogs. Antimicrob Agents Chemother. 2007 Jul;51(7):2430-5. Epub 2007 May 7. [PubMed:17485499 ]
Shi W, Zhang X, Jiang X, Yuan H, Lee JS, Barry CE 3rd, Wang H, Zhang W, Zhang Y: Pyrazinamide inhibits trans-translation in Mycobacterium tuberculosis. Science. 2011 Sep 16;333(6049):1630-2. doi: 10.1126/science.1208813. Epub 2011 Aug 11. [PubMed:21835980 ]

External Links

Resource	Link
Human Metabolome Database (HMDB)	HMDB14483
KEGG Drug	D00144
KEGG Compound	C01956
PubChem Compound	1046
PubChem Substance	46507478
ChemSpider	1017
ChEBI	45285
ChEMBL	CHEMBL614
Therapeutic Targets Database	DAP000660
PharmGKB	PA451182
HET	PZA
Drug Product Database	5937
RxList	http://www.rxlist.com/pyrazinamide-drug.htm
Drugs.com	http://www.drugs.com/cdi/pyrazinamide.html
Wikipedia	Pyrazinamide

ATC Codes

J04AM06 — Rifampicin, pyrazinamide, ethambutol and isoniazid

J04AM05 — Rifampicin, pyrazinamide and isoniazid

J04AK01 — Pyrazinamide

AHFS Codes

08:16.04

PDB Entries

Not Available

FDA label

Not Available

MSDS

Download (73.6 KB)

Clinical Trials

Phase	Status	Purpose	Conditions	Count
0	Recruiting	Treatment	Osteomyelitis	1
1	Completed	Other	Tuberculosis	1
1	Completed	Treatment	Healthy Volunteers	1
1	Completed	Treatment	Human Immunodeficiency Virus (HIV) Infections / Tuberculosis	1
1	Completed	Treatment	Tuberculosis	2
1	Recruiting	Treatment	Tuberculosis	1
1	Terminated	Treatment	Disseminated Neuroblastoma / Recurrent Neuroblastoma	1
1, 2	Recruiting	Treatment	Tuberculous Meningitis	1
2	Active Not Recruiting	Treatment	Human Immunodeficiency Virus (HIV) Infections / Tuberculosis	1
2	Active Not Recruiting	Treatment	Tuberculosis	1
2	Completed	Treatment	Tuberculosis	2
2	Completed	Treatment	Tuberculosis, Pulmonary	5
2	Recruiting	Prevention	Bone destruction / Cancer, Breast	1
2	Recruiting	Treatment	Tuberculosis	1
2	Recruiting	Treatment	Tuberculosis, Multidrug Resistant	1
2	Suspended	Treatment	Tuberculosis, Pulmonary	1
2	Unknown Status	Treatment	Tuberculosis	1
2	Withdrawn	Treatment	Liver Cancer / Metastatic Cancers	1
2, 3	Recruiting	Treatment	Extensively-drug Resistant Tuberculosis / Tuberculosis / Tuberculosis, Multidrug Resistant	1
2, 3	Recruiting	Treatment	Tuberculosis, Pulmonary	1
3	Active Not Recruiting	Treatment	Human Immunodeficiency Virus (HIV) Infections / Tuberculosis, Pulmonary	1
3	Active Not Recruiting	Treatment	Tuberculosis, Pulmonary, Drug Sensitive / Tuberculosis, Pulmonary, Multi Drug-resistant	1
3	Completed	Treatment	Acquired Immune Deficiency Syndrome (AIDS) / Human Immunodeficiency Virus (HIV) Infections / Tuberculosis	1
3	Completed	Treatment	Human Immunodeficiency Virus (HIV) Infections / Tuberculosis	1
3	Completed	Treatment	Tuberculosis	2
3	Not Yet Recruiting	Treatment	Tuberculosis Multi Drug Resistant Active	1
3	Recruiting	Treatment	MDR-TB	1
3	Recruiting	Treatment	Tuberculosis	1
3	Recruiting	Treatment	Tuberculosis, Multidrug Resistant	1
3	Terminated	Treatment	Multiple System Atrophy (MSA)	1
3	Unknown Status	Treatment	Human Immunodeficiency Virus (HIV) Infections / Tuberculosis	1
4	Active Not Recruiting	Prevention	HIV-1 Infections	1
4	Completed	Treatment	Drug Induced Hepatotoxicity / Tuberculosis	1
4	Completed	Treatment	Obstructive Sleep Apnea Syndrome (OSAS)	1
4	Recruiting	Treatment	AIDS With Tuberculosis	1
4	Recruiting	Treatment	Human Immunodeficiency Virus (HIV) Infections	1
4	Recruiting	Treatment	Tuberculosis, Pulmonary	1
4	Recruiting	Treatment	Tuberculosis, Spinal	1
4	Unknown Status	Treatment	Hepatitis / Tuberculosis, Pulmonary	1
4	Unknown Status	Treatment	Reinfection Pulmonary Tuberculosis	1
Not Available	Completed	Prevention	Human Immunodeficiency Virus (HIV) Infections / Tuberculosis	1
Not Available	Completed	Supportive Care	Body Weight Changes / Motor Activities / Tuberculosis, Pulmonary	1
Not Available	Completed	Treatment	Human Immunodeficiency Virus (HIV) Infections / Tuberculosis	3
Not Available	Completed	Treatment	Tuberculosis	1
Not Available	Unknown Status	Not Available	Tuberculosis, Pulmonary	1

Pharmacoeconomics

Manufacturers

Dava pharmaceuticals inc
Mikart inc

Packagers

Amerisource Health Services Corp.
A-S Medication Solutions LLC
Belgomex Sprl
Cardinal Health
Comprehensive Consultant Services Inc.
DAVA Pharmaceuticals
Dept Health Central Pharmacy
Mikart Inc.
Murfreesboro Pharmaceutical Nursing Supply
PCA LLC
PD-Rx Pharmaceuticals Inc.
Physicians Total Care Inc.
Prescript Pharmaceuticals
Remedy Repack
Sanofi-Aventis Inc.
Versapharm Inc.
West-Ward Pharmaceuticals

Dosage forms

Form	Route	Strength
Tablet	Oral	500 mg/1
Tablet	Oral
Tablet, sugar coated	Oral
Tablet	Oral	500 mg

Prices

Unit description	Cost	Unit
Rifater tablet	3.1USD	tablet
Pyrazinamide 500 mg tablet	1.26USD	tablet

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Not Available

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	192 °C	PhysProp
water solubility	1.5E+004 mg/L (at 25 °C)	MERCK INDEX (1996)
logP	-0.60	HANSCH,C ET AL. (1995)
logS	-0.91	ADME Research, USCD
pKa	-0.5	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	93.7 mg/mL	ALOGPS
logP	-0.71	ALOGPS
logP	-1.2	ChemAxon
logS	-0.12	ALOGPS
pKa (Strongest Acidic)	13.06	ChemAxon
pKa (Strongest Basic)	-0.68	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	3	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	68.87 Å²	ChemAxon
Rotatable Bond Count	1	ChemAxon
Refractivity	30.45 m³·mol^-1	ChemAxon
Polarizability	11.13 Å³	ChemAxon
Number of Rings	1	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	No	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Predicted ADMET features

Property	Value	Probability
Human Intestinal Absorption	+	0.9813
Blood Brain Barrier	+	0.9745
Caco-2 permeable	+	0.7222
P-glycoprotein substrate	Non-substrate	0.8219
P-glycoprotein inhibitor I	Non-inhibitor	0.9709
P-glycoprotein inhibitor II	Non-inhibitor	0.9971
Renal organic cation transporter	Non-inhibitor	0.8985
CYP450 2C9 substrate	Non-substrate	0.8861
CYP450 2D6 substrate	Non-substrate	0.876
CYP450 3A4 substrate	Non-substrate	0.7754
CYP450 1A2 substrate	Non-inhibitor	0.8791
CYP450 2C9 inhibitor	Non-inhibitor	0.9545
CYP450 2D6 inhibitor	Non-inhibitor	0.9731
CYP450 2C19 inhibitor	Non-inhibitor	0.9547
CYP450 3A4 inhibitor	Non-inhibitor	0.9697
CYP450 inhibitory promiscuity	Low CYP Inhibitory Promiscuity	0.9353
Ames test	Non AMES toxic	0.9133
Carcinogenicity	Non-carcinogens	0.9321
Biodegradation	Not ready biodegradable	0.9602
Rat acute toxicity	1.8145 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.9939
hERG inhibition (predictor II)	Non-inhibitor	0.9617

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )

Spectra

Mass Spec (NIST)

Download (8.68 KB)

Spectra

Spectrum Type	Description	Splash Key
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS	Not Available
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , positive	splash10-0ab9-1900000000-d29284f74cafc89d62ad	View in MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , positive	splash10-001i-9200000000-f1f9853e24fa676ffa99	View in MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , positive	splash10-001j-9000000000-7be5ab1fa895dc272521	View in MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , positive	splash10-000t-9000000000-9c4235602fdfd2d2cdeb	View in MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , positive	splash10-014i-3009000000-ab4d0160c375af6d52ee	View in MoNA
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	Not Available
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	Not Available
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	Not Available
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	Not Available
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	Not Available
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	Not Available
1D NMR	1H NMR Spectrum	Not Available
1D NMR	13C NMR Spectrum	Not Available

Taxonomy

Description

This compound belongs to the class of chemical entities known as pyrazines. These are compounds containing a pyrazine ring, which is a six-member aromatic heterocycle, that consists of two nitrogen atoms (at positions 1 and 4) and four carbon atoms.

Kingdom

Chemical entities

Super Class

Organic compounds

Class

Organoheterocyclic compounds

Sub Class

Diazines

Direct Parent

Pyrazines

Alternative Parents

Heteroaromatic compounds / Carboximidic acids / Azacyclic compounds / Organopnictogen compounds / Organooxygen compounds / Organonitrogen compounds / Hydrocarbon derivatives

Substituents

Pyrazine / Heteroaromatic compound / Azacycle / Carboximidic acid derivative / Carboximidic acid / Organic nitrogen compound / Organic oxygen compound / Organopnictogen compound / Hydrocarbon derivative / Organooxygen compound

Molecular Framework

Aromatic heteromonocyclic compounds

External Descriptors

pyrazines, monocarboxylic acid amide (CHEBI:45285 ) / a carboxamide (PYRAZINAMIDE )

Targets

1. Fatty acid synthetase I (FASI)

Kind: Protein
Organism: Mycobacterium tuberculosis
Pharmacological action: yes
Actions: inhibitor

References

Zimhony O, Cox JS, Welch JT, Vilcheze C, Jacobs WR Jr: Pyrazinamide inhibits the eukaryotic-like fatty acid synthetase I (FASI) of Mycobacterium tuberculosis. Nat Med. 2000 Sep;6(9):1043-7. [PubMed:10973326 ]
Ngo SC, Zimhony O, Chung WJ, Sayahi H, Jacobs WR Jr, Welch JT: Inhibition of isolated Mycobacterium tuberculosis fatty acid synthase I by pyrazinamide analogs. Antimicrob Agents Chemother. 2007 Jul;51(7):2430-5. Epub 2007 May 7. [PubMed:17485499 ]
Zimhony O, Vilcheze C, Arai M, Welch JT, Jacobs WR Jr: Pyrazinoic acid and its n-propyl ester inhibit fatty acid synthase type I in replicating tubercle bacilli. Antimicrob Agents Chemother. 2007 Feb;51(2):752-4. Epub 2006 Nov 13. [PubMed:17101678 ]
Schroeder EK, de Souza N, Santos DS, Blanchard JS, Basso LA: Drugs that inhibit mycolic acid biosynthesis in Mycobacterium tuberculosis. Curr Pharm Biotechnol. 2002 Sep;3(3):197-225. [PubMed:12164478 ]

Enzymes

Details

1. Xanthine dehydrogenase/oxidase

Kind: Protein
Organism: Human
Pharmacological action: unknown
Actions: substrate

General Function:: Xanthine oxidase activity
Specific Function:: Key enzyme in purine degradation. Catalyzes the oxidation of hypoxanthine to xanthine. Catalyzes the oxidation of xanthine to uric acid. Contributes to the generation of reactive oxygen species. Has also low oxidase activity towards aldehydes (in vitro).
Gene Name:: XDH
Uniprot ID:: P47989
Uniprot Name:: Xanthine dehydrogenase/oxidase
Molecular Weight:: 146422.99 Da

References

Moriwaki Y, Yamamoto T, Nasako Y, Takahashi S, Suda M, Hiroishi K, Hada T, Higashino K: In vitro oxidation of pyrazinamide and allopurinol by rat liver aldehyde oxidase. Biochem Pharmacol. 1993 Sep 14;46(6):975-81. [PubMed:8216357 ]

Details

2. Aldehyde oxidase

Kind: Protein
Organism: Human
Pharmacological action: unknown
Actions: substrate

General Function:: Xanthine dehydrogenase activity
Specific Function:: Oxidase with broad substrate specificity, oxidizing aromatic azaheterocycles, such as N1-methylnicotinamide and N-methylphthalazinium, as well as aldehydes, such as benzaldehyde, retinal, pyridoxal, and vanillin. Plays a key role in the metabolism of xenobiotics and drugs containing aromatic azaheterocyclic substituents. Participates in the bioactivation of prodrugs such as famciclovir, catalyz...
Gene Name:: AOX1
Uniprot ID:: Q06278
Uniprot Name:: Aldehyde oxidase
Molecular Weight:: 147916.735 Da

References

Moriwaki Y, Yamamoto T, Nasako Y, Takahashi S, Suda M, Hiroishi K, Hada T, Higashino K: In vitro oxidation of pyrazinamide and allopurinol by rat liver aldehyde oxidase. Biochem Pharmacol. 1993 Sep 14;46(6):975-81. [PubMed:8216357 ]

Details

3. Cytochrome P450 1A2

Kind: Protein
Organism: Human
Pharmacological action: unknown
Actions: substrate

General Function:: Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function:: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N...
Gene Name:: CYP1A2
Uniprot ID:: P05177
Uniprot Name:: Cytochrome P450 1A2
Molecular Weight:: 58293.76 Da

References

Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]

Details

4. Cytochrome P450 3A4

Kind: Protein
Organism: Human
Pharmacological action: unknown
Actions: substrate

General Function:: Vitamin d3 25-hydroxylase activity
Specific Function:: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:: CYP3A4
Uniprot ID:: P08684
Uniprot Name:: Cytochrome P450 3A4
Molecular Weight:: 57342.67 Da

References

Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]

Drug created on June 13, 2005 07:24 / Updated on July 18, 2017 16:48

Get DrugBank to go!

Structure for DB00339 (Pyrazinamide)

Targets

References

Enzymes

References

References

References

References