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Details

Stereochemistry ACHIRAL
Molecular Formula C5H5N3O
Molecular Weight 123.1127
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PYRAZINAMIDE

SMILES

NC(=O)C1=CN=CC=N1

InChI

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

HIDE SMILES / InChI

Molecular Formula C5H5N3O
Molecular Weight 123.1127
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: description was created based on several sources, including: http://www.drugbank.ca/drugs/DB00339 https://en.wikipedia.org/wiki/Pyrazinamide

Pyrazinamide is indicated for the initial treatment of active tuberculosis in adults and children when combined with other antituberculous agents. (The current recommendation of the CDC for drug-susceptible disease is to use a six-month regimen for initial treatment of active tuberculosis, consisting of isoniazid, rifampin and pyrazinamide given for 2 months, followed by isoniazid and rifampin for 4 months. Pyrazinamide should only be used in conjunction with other effective antituberculous agents. 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. 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 . 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. 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

CNS Activity

Curator's Comment: Drugs like isoniazid, pyrazinamide and cycloserine cross the blood brain barrier (BBB) freely, but the behavior of rifampicin, ethambutol and streptomycin is less predictable in the presence of inflamed meninges. The CSF concentration of these drugs is at least equal to or higher than those in the noninflamed meninges

Originator

Curator's Comment: The discovery of pyrazinamide was announced by Kushner and coworkers of Lederle Laboratories in 1952

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
PYRAZINAMIDE

Approved Use

Pyrazinamide

Launch Date

1971
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
38.2 mg/L
27.8 mg/kg bw 3 times / day steady-state, oral
dose: 27.8 mg/kg bw
route of administration: Oral
experiment type: STEADY-STATE
co-administered: Isoniazid | Rifampicin | Ethambutol
PYRAZINAMIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
38.7 mg/L
27 mg/kg bw single, oral
dose: 27 mg/kg bw
route of administration: Oral
experiment type: SINGLE
co-administered:
PYRAZINAMIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
344 mg × h/mL
27.8 mg/kg bw 3 times / day steady-state, oral
dose: 27.8 mg/kg bw
route of administration: Oral
experiment type: STEADY-STATE
co-administered: Isoniazid | Rifampicin | Ethambutol
PYRAZINAMIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
520 mg × h/L
27 mg/kg bw single, oral
dose: 27 mg/kg bw
route of administration: Oral
experiment type: SINGLE
co-administered:
PYRAZINAMIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
5.5 h
27.8 mg/kg bw 3 times / day steady-state, oral
dose: 27.8 mg/kg bw
route of administration: Oral
experiment type: STEADY-STATE
co-administered: Isoniazid | Rifampicin | Ethambutol
PYRAZINAMIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
1500 mg 1 times / day multiple, oral
Recommended
Dose: 1500 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1500 mg, 1 times / day
Co-administed with::
ofloxacin, p.o(800 mg/day; 6 months)
Sources:
healthy
n = 16
Health Status: healthy
Population Size: 16
Sources:
Disc. AE: Arthralgia, Distress gastrointestinal...
AEs leading to
discontinuation/dose reduction:
Arthralgia (43.75%)
Distress gastrointestinal (37.5%)
Pruritus (25%)
Fatigue (25%)
Generalized maculopapular rash (18.8%)
Insomnia (18.8%)
Vertigo (12.5%)
Sources:
20 mg/kg 1 times / day multiple, oral
Recommended
Dose: 20 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg/kg, 1 times / day
Co-administed with::
rifampin, p.o(600 mg/d; 2 months)
Sources: Page: p.643
unhealthy
n = 207
Health Status: unhealthy
Condition: Tuberculosis
Sex: M+F
Population Size: 207
Sources: Page: p.643
Disc. AE: Hepatotoxicity...
AEs leading to
discontinuation/dose reduction:
Hepatotoxicity (5.8%)
Sources: Page: p.643
30 mg/kg 1 times / day multiple, oral (max)
Recommended
unhealthy
Disc. AE: Hepatotoxicity...
AEs

AEs

AESignificanceDosePopulation
Vertigo 12.5%
Disc. AE
1500 mg 1 times / day multiple, oral
Recommended
Dose: 1500 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1500 mg, 1 times / day
Co-administed with::
ofloxacin, p.o(800 mg/day; 6 months)
Sources:
healthy
n = 16
Health Status: healthy
Population Size: 16
Sources:
Generalized maculopapular rash 18.8%
Disc. AE
1500 mg 1 times / day multiple, oral
Recommended
Dose: 1500 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1500 mg, 1 times / day
Co-administed with::
ofloxacin, p.o(800 mg/day; 6 months)
Sources:
healthy
n = 16
Health Status: healthy
Population Size: 16
Sources:
Insomnia 18.8%
Disc. AE
1500 mg 1 times / day multiple, oral
Recommended
Dose: 1500 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1500 mg, 1 times / day
Co-administed with::
ofloxacin, p.o(800 mg/day; 6 months)
Sources:
healthy
n = 16
Health Status: healthy
Population Size: 16
Sources:
Fatigue 25%
Disc. AE
1500 mg 1 times / day multiple, oral
Recommended
Dose: 1500 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1500 mg, 1 times / day
Co-administed with::
ofloxacin, p.o(800 mg/day; 6 months)
Sources:
healthy
n = 16
Health Status: healthy
Population Size: 16
Sources:
Pruritus 25%
Disc. AE
1500 mg 1 times / day multiple, oral
Recommended
Dose: 1500 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1500 mg, 1 times / day
Co-administed with::
ofloxacin, p.o(800 mg/day; 6 months)
Sources:
healthy
n = 16
Health Status: healthy
Population Size: 16
Sources:
Distress gastrointestinal 37.5%
Disc. AE
1500 mg 1 times / day multiple, oral
Recommended
Dose: 1500 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1500 mg, 1 times / day
Co-administed with::
ofloxacin, p.o(800 mg/day; 6 months)
Sources:
healthy
n = 16
Health Status: healthy
Population Size: 16
Sources:
Arthralgia 43.75%
Disc. AE
1500 mg 1 times / day multiple, oral
Recommended
Dose: 1500 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1500 mg, 1 times / day
Co-administed with::
ofloxacin, p.o(800 mg/day; 6 months)
Sources:
healthy
n = 16
Health Status: healthy
Population Size: 16
Sources:
Hepatotoxicity 5.8%
Disc. AE
20 mg/kg 1 times / day multiple, oral
Recommended
Dose: 20 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg/kg, 1 times / day
Co-administed with::
rifampin, p.o(600 mg/d; 2 months)
Sources: Page: p.643
unhealthy
n = 207
Health Status: unhealthy
Condition: Tuberculosis
Sex: M+F
Population Size: 207
Sources: Page: p.643
Hepatotoxicity Disc. AE
30 mg/kg 1 times / day multiple, oral (max)
Recommended
unhealthy
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
A new class of antituberculosis agents.
2000 Aug 24
pncA mutations as a major mechanism of pyrazinamide resistance in Mycobacterium tuberculosis: spread of a monoresistant strain in Quebec, Canada.
2000 Mar
Pancreatic mass caused by Mycobacterium tuberculosis with reduced drug sensitivity.
2001 Apr
Utility of PCR assays for rapid diagnosis of BCG infection in children.
2001 Apr
[Functional role of the red nucleus in the cerebral cortex-cerebellum-spinal cord communication system].
2001 Apr-Jun
The role of passive immunization in hiv-positive patients : a case report.
2001 Aug
[Effectiveness and problems of PZA-containing 6-month regimen for the treatment of new pulmonary tuberculosis patients].
2001 Jan
Bioisosteres of 9-carboxymethyl-4-oxo-imidazo[1,2-a]indeno-[1,2-e]pyrazin-2-carboxylic acid derivatives. Progress towards selective, potent in vivo AMPA antagonists with longer durations of action.
2001 Jan 22
[Central nervous system tuberculosis in children: 2. Treatment and outcome].
2001 Mar
Diagnosis and treatment of isolated tuberculous mediastinal lymphadenopathy in adults.
2001 May
Antimycobacterial plant terpenoids.
2001 Nov
Tuberculous meningitis: is a 6-month treatment regimen sufficient?
2001 Nov
Rapamycin and less immunosuppressive analogs are toxic to Candida albicans and Cryptococcus neoformans via FKBP12-dependent inhibition of TOR.
2001 Nov
Treatment of tuberculosis in Haiti.
2001 Oct
Susceptibility testing of Mycobacterium tuberculosis to pyrazinamide.
2002 Jan
Patents

Patents

Sample Use Guides

In Vivo Use Guide
Curator's Comment: Three grams per day should not be exceeded. The CDC (Center for Disease Control ) recommendations do not exceed 2 g per day when given as a daily regimen
15 to 30 mg/kg once daily
Route of Administration: Oral
In Vitro Use Guide
Unknown
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:22:42 GMT 2023
Edited
by admin
on Fri Dec 15 15:22:42 GMT 2023
Record UNII
2KNI5N06TI
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
PYRAZINAMIDE
EP   HSDB   INN   MART.   MI   ORANGE BOOK   USP   USP-RS   VANDF   WHO-DD   WHO-IP  
INN  
Official Name English
PYRAZINAMIDE [USP-RS]
Common Name English
D-50
Code English
PYRAZIDE
Common Name English
PYRAZINAMIDE [MART.]
Common Name English
PYRAZINAMIDE COMPONENT OF RIFATER
Common Name English
PYRAZINAMIDE [HSDB]
Common Name English
PYRAZINAMIDE [USP MONOGRAPH]
Common Name English
PYRAFAT
Common Name English
PYRAMIZADE
Common Name English
PIRAZINAMID
Common Name English
PYRAZINAMIDE [MI]
Common Name English
RIFATER COMPONENT PYRAZINAMIDE
Common Name English
Pyrazinecarboxamide
Systematic Name English
PYRAZINAMIDE [JAN]
Common Name English
ZINAMIDE
Common Name English
ALDINAMID
Common Name English
NOVAMID
Common Name English
PYRAZINAMIDE [VANDF]
Common Name English
ALDINAMIDE
Common Name English
PYRAZINAMIDE [USP IMPURITY]
Common Name English
FARMIZINA
Common Name English
NSC-14911
Code English
pyrazinamide [INN]
Common Name English
PYRAZINAMIDE [ORANGE BOOK]
Common Name English
UNIPYRANAMIDE
Common Name English
PIRAZIMIDA
Common Name English
PYRAZINAMIDUM [WHO-IP LATIN]
Common Name English
PYRAZINAMIDE [EP MONOGRAPH]
Common Name English
MK-56
Code English
PYRAZINE CARBOXYLAMIDE
Common Name English
.ALPHA.-PYRAZINAMIDE
Common Name English
ISOPAS
Common Name English
PYRAZINAMIDE [WHO-IP]
Common Name English
ROZIDE
Common Name English
TEBRAZID
Common Name English
Pyrazinamide [WHO-DD]
Common Name English
EPRAZIN
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C280
Created by admin on Fri Dec 15 15:22:42 GMT 2023 , Edited by admin on Fri Dec 15 15:22:42 GMT 2023
WHO-VATC QJ04AM05
Created by admin on Fri Dec 15 15:22:42 GMT 2023 , Edited by admin on Fri Dec 15 15:22:42 GMT 2023
WHO-ESSENTIAL MEDICINES LIST 6.2.4 (ISO/PYR/RIF)
Created by admin on Fri Dec 15 15:22:42 GMT 2023 , Edited by admin on Fri Dec 15 15:22:42 GMT 2023
WHO-ATC J04AM06
Created by admin on Fri Dec 15 15:22:42 GMT 2023 , Edited by admin on Fri Dec 15 15:22:42 GMT 2023
WHO-ATC J04AK01
Created by admin on Fri Dec 15 15:22:42 GMT 2023 , Edited by admin on Fri Dec 15 15:22:42 GMT 2023
WHO-ATC J04AM05
Created by admin on Fri Dec 15 15:22:42 GMT 2023 , Edited by admin on Fri Dec 15 15:22:42 GMT 2023
WHO-ESSENTIAL MEDICINES LIST 6.2.4 (ETH/ISO/PYR/RIF)
Created by admin on Fri Dec 15 15:22:42 GMT 2023 , Edited by admin on Fri Dec 15 15:22:42 GMT 2023
WHO-ESSENTIAL MEDICINES LIST 6.2.4
Created by admin on Fri Dec 15 15:22:42 GMT 2023 , Edited by admin on Fri Dec 15 15:22:42 GMT 2023
WHO-VATC QJ04AM06
Created by admin on Fri Dec 15 15:22:42 GMT 2023 , Edited by admin on Fri Dec 15 15:22:42 GMT 2023
LIVERTOX NBK547856
Created by admin on Fri Dec 15 15:22:42 GMT 2023 , Edited by admin on Fri Dec 15 15:22:42 GMT 2023
NDF-RT N0000175483
Created by admin on Fri Dec 15 15:22:42 GMT 2023 , Edited by admin on Fri Dec 15 15:22:42 GMT 2023
WHO-VATC QJ04AK01
Created by admin on Fri Dec 15 15:22:42 GMT 2023 , Edited by admin on Fri Dec 15 15:22:42 GMT 2023
FDA ORPHAN DRUG 6585
Created by admin on Fri Dec 15 15:22:42 GMT 2023 , Edited by admin on Fri Dec 15 15:22:42 GMT 2023
Code System Code Type Description
EPA CompTox
DTXSID9021215
Created by admin on Fri Dec 15 15:22:42 GMT 2023 , Edited by admin on Fri Dec 15 15:22:42 GMT 2023
PRIMARY
ChEMBL
CHEMBL614
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PRIMARY
DRUG CENTRAL
2328
Created by admin on Fri Dec 15 15:22:42 GMT 2023 , Edited by admin on Fri Dec 15 15:22:42 GMT 2023
PRIMARY
LACTMED
Pyrazinamide
Created by admin on Fri Dec 15 15:22:42 GMT 2023 , Edited by admin on Fri Dec 15 15:22:42 GMT 2023
PRIMARY
WIKIPEDIA
PYRAZINAMIDE
Created by admin on Fri Dec 15 15:22:42 GMT 2023 , Edited by admin on Fri Dec 15 15:22:42 GMT 2023
PRIMARY
WHO INTERNATIONAL PHARMACOPEIA
PYRAZINAMIDE
Created by admin on Fri Dec 15 15:22:42 GMT 2023 , Edited by admin on Fri Dec 15 15:22:42 GMT 2023
PRIMARY Description: A white or almost white, crystalline powder; odourless. Solubility: Sparingly soluble in water; slightly soluble in ethanol (~750 g/l) TS. Category: Antituberculosis drug. Storage: Pyrazinamide should be kept in a well-closed container. Definition: Pyrazinamide contains not less than 98.5% and not more than 101.0% of C5H5N3O, calculated with reference to the anhydrous substance.
ECHA (EC/EINECS)
202-717-6
Created by admin on Fri Dec 15 15:22:42 GMT 2023 , Edited by admin on Fri Dec 15 15:22:42 GMT 2023
PRIMARY
PUBCHEM
1046
Created by admin on Fri Dec 15 15:22:42 GMT 2023 , Edited by admin on Fri Dec 15 15:22:42 GMT 2023
PRIMARY
EVMPD
SUB10163MIG
Created by admin on Fri Dec 15 15:22:42 GMT 2023 , Edited by admin on Fri Dec 15 15:22:42 GMT 2023
PRIMARY
INN
786
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PRIMARY
IUPHAR
7287
Created by admin on Fri Dec 15 15:22:42 GMT 2023 , Edited by admin on Fri Dec 15 15:22:42 GMT 2023
PRIMARY
MESH
D011718
Created by admin on Fri Dec 15 15:22:42 GMT 2023 , Edited by admin on Fri Dec 15 15:22:42 GMT 2023
PRIMARY
HSDB
3576
Created by admin on Fri Dec 15 15:22:42 GMT 2023 , Edited by admin on Fri Dec 15 15:22:42 GMT 2023
PRIMARY
DAILYMED
2KNI5N06TI
Created by admin on Fri Dec 15 15:22:42 GMT 2023 , Edited by admin on Fri Dec 15 15:22:42 GMT 2023
PRIMARY
NSC
14911
Created by admin on Fri Dec 15 15:22:42 GMT 2023 , Edited by admin on Fri Dec 15 15:22:42 GMT 2023
PRIMARY
CHEBI
45285
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PRIMARY
SMS_ID
100000080846
Created by admin on Fri Dec 15 15:22:42 GMT 2023 , Edited by admin on Fri Dec 15 15:22:42 GMT 2023
PRIMARY
DRUG BANK
DB00339
Created by admin on Fri Dec 15 15:22:42 GMT 2023 , Edited by admin on Fri Dec 15 15:22:42 GMT 2023
PRIMARY
CAS
98-96-4
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PRIMARY
RXCUI
8987
Created by admin on Fri Dec 15 15:22:42 GMT 2023 , Edited by admin on Fri Dec 15 15:22:42 GMT 2023
PRIMARY RxNorm
MERCK INDEX
m9337
Created by admin on Fri Dec 15 15:22:42 GMT 2023 , Edited by admin on Fri Dec 15 15:22:42 GMT 2023
PRIMARY Merck Index
RS_ITEM_NUM
1585006
Created by admin on Fri Dec 15 15:22:42 GMT 2023 , Edited by admin on Fri Dec 15 15:22:42 GMT 2023
PRIMARY
FDA UNII
2KNI5N06TI
Created by admin on Fri Dec 15 15:22:42 GMT 2023 , Edited by admin on Fri Dec 15 15:22:42 GMT 2023
PRIMARY
NCI_THESAURUS
C29395
Created by admin on Fri Dec 15 15:22:42 GMT 2023 , Edited by admin on Fri Dec 15 15:22:42 GMT 2023
PRIMARY
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PARENT -> CONSTITUENT ALWAYS PRESENT
MIC value of the in vitro growth of Mycobacterium Tuberculosis (H37RV strain) of the new anti-tuberculosis terpenoid derived agent tested was 20 ug/ml.
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