ChemicalBook
Chinese Japanese Germany Korea

Pyrazinamide

Anti-tuberculosis drug Drug Interactions Indications Dosage First aid treatment Adverse reactions and side effects Uses
Pyrazinamide
Pyrazinamide structure
CAS No.
98-96-4
Chemical Name:
Pyrazinamide
Synonyms
PZA;PZAD;mk56;MK 56;T 165;Eprazin;Novamid;Pyrafat;Tisamid;Tebrazid
CBNumber:
CB7429387
Molecular Formula:
C5H5N3O
Formula Weight:
123.11
MOL File:
98-96-4.mol

Pyrazinamide Properties

Melting point:
189-191 °C(lit.)
Boiling point:
229.19°C (rough estimate)
Density 
1.3260 (rough estimate)
refractive index 
1.5900 (estimate)
Flash point:
>110°(230°F)
storage temp. 
-20°C Freezer
solubility 
H2O: soluble50mg/mL
form 
Crystalline Powder or Needles
pka
0.5(at 25℃)
color 
White
PH
7 (H2O)
Water Solubility 
15 mg/mL
Merck 
14,7956
BRN 
112306
CAS DataBase Reference
98-96-4(CAS DataBase Reference)
NIST Chemistry Reference
Pyrazine carboxamide(98-96-4)
EPA Substance Registry System
Pyrazinecarboxamide(98-96-4)

SAFETY

Hazard Codes  F,C
Risk Statements  11-34
Safety Statements  22-24/25-45-36/37/39-26-16
WGK Germany  3
RTECS  UQ2275000
TSCA  Yes
HS Code  29339990
Hazardous Substances Data 98-96-4(Hazardous Substances Data)

Pyrazinamide price More Price(15)

Manufacturer Product number Product description CAS number Packaging Price Updated Buy
Sigma-Aldrich 40751 Pyrazinecarboxamide analytical standard 98-96-4 100mg $51.5 2018-11-13 Buy
Sigma-Aldrich 1585006 Pyrazinamide United States Pharmacopeia (USP) Reference Standard 98-96-4 200mg $348 2018-11-13 Buy
TCI Chemical P0633 Pyrazinamide >98.0%(HPLC)(N) 98-96-4 25g $52 2018-11-22 Buy
Alfa Aesar J66822 Pyrazinamide, 98% 98-96-4 25g $53.9 2018-11-13 Buy
Alfa Aesar J66822 Pyrazinamide, 98% 98-96-4 10g $36.9 2018-11-13 Buy

Pyrazinamide Chemical Properties,Uses,Production

Anti-tuberculosis drug

Pyrazinamide is a second-line anti-tuberculosis drug, also known as formamide pyrazine, carbamoyl pyrazine, and isonicotinic acid amine. At room temperature, it appears as a white crystalline powder and is slightly soluble in water and is odorless with slightly bitter taste. It has a good antibacterial effect against human type Mycobacterium tuberculosis with the strongest bactericidal effect at the range of pH value being between 5-5.5. It has especially optimal bactericidal effect against the Mycobacterium tuberculosis inside the slow-growing phagocytic cells in acidic environment. After pyrazinamide penetrates into the phagocytic cells and enter into the body of Mycobacterium tuberculosis, lactamase in vivo make it be de-amidated, being converted to pyrazine acid to play the antibacterial effect.
The in vivo inhibitory concentration is 12.5μg/ml with the concentration of 50 μg/ml being able to kill the Mycobacterium tuberculosis. The inhibitory concentration against Mycobacterium tuberculosis in vivo is 10 times lower than that in vitro with almost no inhibitory effect in a neutral, alkaline environment.
Its anti-bacterial effect is between streptomycin and paramisansodium. It has great toxicity and can easy to produce drug resistance and should be used in combination with other anti-TB drugs.
Pyrazinamide has similar chemical structure with nicotinamide and can interfere with the dehydrogenase through substitution of nicotinamide, therefore preventing the dehydrogenation and inhibiting the utilization of oxygen by Mycobacterium tuberculosis, causing death of the bacteria due to failure of normal metabolism.
It is oral easily absorbed and is widely distributed in body tissues and fluids including liver, lung, cerebrospinal fluid, kidney and bile. After 2 hours, its plasma concentration can reach peak. The concentration of cerebrospinal fluid is similar as blood concentrations. It can subject to hepatic metabolism to be hydrolyzed to the pyrazine acid that is a kind of metabolite having antimicrobial activity, then further being hydroxylated into inactive metabolites and excreted in urine after glomerular filtration. The t1/2 is about 8 to 10 hours. It can be used in combination with other kind of anti-TB drugs fro the treatment of some complex cases of tuberculosis and tubercular meningitis patients.

Drug Interactions

1, when being combined with allopurinol, colchicine, probenecid, and sulfinpyrazone, pyrazinamide can increase the serum uric acid concentration and further reduce the efficacy of the above drugs on gout. Therefore, when being combined with pyrazinamide, the above drugs should be subject to dose adjustment in order to control hyperuricemia and gout.
2, it can enhance the adverse reactions when combined with B sulfur isonicotinoyl amine.
3, when cyclosporine is used simultaneously with pyrazinamide, the blood concentration of the former drug may be reduced, and therefore the blood concentration needs to be monitored and we should adjust the dose if necessary.
4, it has synergistic effect when combined with isoniazid and rifampin and can delay the development of drug resistance.
The above information is edited by the chemicalbook of Dai Xiongfeng.

Indications

It can be used in combination with other anti-TB drugs for the treatment of tuberculosis that failed to be cured by first-line anti-TB drugs (such as streptomycin, isoniazid, rifampicin and ethambutol).
This product is only valid against mycobacteria.
In the past, pyrazinamide was used as second-line drugs, commonly applied to the patients undergoing retirement due to failure to be cured by other anti-TB drugs. A large number of clinical studies have shown: the short course regimen containing this product is suitable for being applied to the newly diagnosed sputum-positive cases. It is generally applied for 2 to 3 months. This protocol can enable a significant reduction of the re-positive rate of Mycobacterium tuberculosis after the end of treatment.
This product has been well considered as the composition of triple or quadruple protocols in short course chemotherapy.

Dosage

When used in combination therapy with other anti-TB drugs, the common dose of adult oral administration is: every 6 hours according to the weight 5-8.75mg/kg, or every eight hours according to the weight 6.7-11.7mg/kg; the highest value is 3 g daily.
Upon treatment of the infection of isoniazid resistant bacteria, you can increase the dose to 60 mg/kg daily.
Children should take with caution, the necessary reference amount should be: 20-25mg/kg daily, it should be separately orally administrated in 3 times with the maximum dose being 2 g daily, the treatment course is generally 2 to 3 months, it can not be more than six months.

First aid treatment

1. Misusage patients should be immediately subject to gastric lavage and catharsis.
2. If liver dysfunction occurs during the course of treatment, the drug should be discontinued and routine liver-protection therapy should be applied.
3. Patients of gout should be given 0.25g/time probenecid (carboxymethyl benzene with oral administration in 3 times daily and being able to promote the excretion of uric acid.
4. Allergic patients should be given treatment with antihistamines and corticosteroids.

Adverse reactions and side effects

Long-term or high-dose application of the product is easy to cause liver damage and increased blood uric acid and can also cause gastrointestinal irritation and allergic reactions.
For patients of relative high incidence: loss of appetite, fever, unusual fatigue or weakness, yellowing of the eyes or skin (liver toxicity).
Persons of low incidence: chills, joint pain (especially in the big toe, the condyle, knee) or diseased joints skin taut fever (acute gouty joint pain).
During the treatment course of this drug, the blood uric acid can increase and can cause acute gout that should be subject to determination of serum uric acid.
Adverse reactions are dose-related. After current application of conventional dosage, adverse reactions have been rarely observed.
Hepatic impairment: administration of drug for 3g daily with about 15% of patients getting liver damage, hepatomegaly, tenderness, elevated transaminases and jaundice. Currently upon applying 1.5 g daily for a 3-month treatment course, reactions of liver toxicity are rare.
Joint pain: PZA metabolites can inhibit the excretion of uric acid, causing hyperuricemia and gout-like performance with resumption after stopping drug.
Gastrointestinal reactions: loss of appetite, nausea, vomiting.
Allergies: occasionally fever and rash, and even jaundice.
Skin reactions: in some individual cases, the patients are light sensitive with the exposed parts of the skin being bright red brown. Patients subject to the long-term medication have their skins be bronze that can be gradually restored after the withdrawal of the drug. For diabetic patients taking pyrazinamide, it is difficult to control the level of blood sugar.

Uses

It is a kind of anti-tuberculosis drugs.

Chemical Properties

Crystalline Solid

Uses

An antibacterial agent used to study liver toxicity prevention

Uses

Antibacterial (tuberculostatic)

Indications

Pyrazinamide is a synthetic analogue of nicotinamide. Its exact mechanism of action is not known, although its target appears to be the mycobacterial fatty acid synthetase involved in mycolic acid biosynthesis. Pyrazinamide requires an acidic environment, such as that found in the phagolysosomes, to express its tuberculocidal activity. Thus, pyrazinamide is highly effective on intracellular mycobacteria. The mycobacterial enzyme pyrazinamidase converts pyrazinamide to pyrazinoic acid, the active form of the drug.A mutation in the gene (pncA) that encodes pyrazinamidase is responsible for drug resistance; resistance can be delayed through the use of drug combination therapy.

Antimicrobial activity

It is principally active against actively metabolizing intracellular bacilli and those in acidic, anoxic inflammatory lesions. Activity against M. tuberculosis is highly pH dependent: at pH 5.6 the MIC is 8–16 mg/L, but it is almost inactive at neutral pH. Other mycobacterial species, including M. bovis, are resistant. Activity requires conversion to pyrazinoic acid by the mycobacterial enzyme pyrazinamidase, encoded for by the pncA gene, which is present in M. tuberculosis but not M. bovis. A few resistant strains lack mutations in pncA, indicating alternative mechanisms for resistance, including defects in transportation of the agent into the bacterial cell.

Acquired resistance

Drug resistance is uncommon and cross-resistance to other antituberculosis agents does not occur. Susceptibility testing is technically demanding as it requires very careful control of the pH of the medium, but molecular methods for detection of resistance-conferring mutations are available.

General Description

Pyrazinecarboxamide (PZA) occurs as a white crystalline powder that is sparingly soluble in water and slightly soluble in polar organic solvents. Its antitubercular properties were discovered as a result of an investigation of heterocyclic analogs of nicotinic acid, with which it is isosteric. Pyrazinamide has recently been elevated to first-line status in short-term tuberculosis treatment regimens because of its tuberculocidal activity and comparatively low short-term toxicity. Since pyrazinamide is not active against metabolically inactive tubercle bacilli, it is not considered suitable for long-term therapy. Potential hepatotoxicity also obviates long-term use of the drug. Pyrazinamide is maximally effective in the low pH environment that exists in macrophages (monocytes). Evidence suggests bioactivation of pyrazinamide to pyrazinoic acid by an amidase present in mycobacteria.

General Description

White powder. Sublimes from 318°F.

Air & Water Reactions

Water soluble.

Reactivity Profile

Pyrazinamide is a carbamate ester. Incompatible with strong acids and bases, and especially incompatible with strong reducing agents such as hydrides. May react with active metals or nitrides to produce flammable gaseous hydrogen. Incompatible with strongly oxidizing acids, peroxides, and hydroperoxides.

Pharmaceutical Applications

Like isoniazid, pyrazinamide is a synthetic nicotinamide analog, although its mode of action is quite distinct.

Pharmacology

Pyrazinamide is well absorbed from the GI tract and is widely distributed throughout the body. It penetrates tissues, macrophages, and tuberculous cavities and has excellent activity on the intracellular organisms; its plasma half-life is 9 to 10 hours in patients with normal renal function. The drug and its metabolites are excreted primarily by renal glomerular filtration.

Pharmacokinetics

Oral absorption: >90%
Cmax 20–22 mg/kg oral: 10–50 mg/L after 2 h
Plasma half-life: c. 9 h
Plasma protein binding: c. 50%
It readily crosses the blood–brain barrier, achieving CSF concentrations similar to plasma levels. It is metabolized to pyrazinoic acid in the liver and oxidized to inactive metabolites, which are excreted in the urine, although about 70% of an oral dose is excreted unchanged.

Clinical Use

Tuberculosis (a component of the early, intensive phase of short-course therapy)

Clinical Use

Pyrazinamide is an essential component of the multidrug short-term therapy of tuberculosis. In combination with isoniazid and rifampin, it is active against the intracellular organisms that may cause relapse.

Side effects

It is usually well tolerated. Moderate elevations of serum transaminases occur early in treatment. Severe hepatotoxicity is uncommon with standard dosage, except in patients with pre-existing liver disease.
Its principal metabolite, pyrazinoic acid, inhibits renal excretion of uric acid, but gout is extremely rare. An unrelated arthralgia, notably of the shoulders and responsive to analgesics, also occurs.
Other side effects include anorexia, nausea, mild flushing of the skin and photosensitization.

Side effects

Hepatotoxicity is the major concern in 15% of pyrazinamide recipients. It also can inhibit excretion of urates, resulting in hyperuricemia. Nearly all patients taking pyrazinamide develop hyperuricemia and possibly acute gouty arthritis. Other adverse effects include nausea, vomiting, anorexia, drug fever, and malaise. Pyrazinamide is not recommended for use during pregnancy.

Enzyme inhibitor

This pyrazinecarboxamide (FW = 123.11 g/mol), is an important tuberculosis-sterilizing drug that helps to shorten the duration of current chemotherapy regimens for tuberculosis. Pyrazinamide, which is hydrolyzed by an amidase to pyrazinoic acid, has a pKa value of 0.5 and is soluble in water (15 mg/mL). Key Pharmacokinetic Parameters: See Appendix II in Goodman & Gilman’s THE PHARMACOLOGICAL BASIS OF THERAPEUTICS, 12th Edition (Brunton, Chabner & Knollmann, eds.) McGraw-Hill Medical, New York. Target (s) : fatty-acid synthase ; NAD+ ADP-ribosyltransferase, or poly (ADP-ribose) polymerase, IC50 = 0.13 mM; nicotinamidase, also alternative substrate; and nicotinate N-methyltransferase.

Purification Methods

The amide crystallises from water, EtOH or 1:1 hexane/EtOH in four modifications viz -form, -form, -form and form. [R. & S.rum Acta Cryst 28B 1677 1972, Beilstein 25 III/IV 772.]

Pyrazinamide Preparation Products And Raw materials

Raw materials

Preparation Products


Pyrazinamide Suppliers

Global( 252)Suppliers
Supplier Tel Fax Email Country ProdList Advantage
Shenzhen Sendi Biotechnology Co.Ltd.
0755-23311925 18102838259
0755-23311925 Abel@chembj.com CHINA 3203 55
Henan DaKen Chemical CO.,LTD.
+86-371-55531817
info@dakenchem.com CHINA 21930 58
Henan Tianfu Chemical Co.,Ltd.
0371-55170693
0371-55170693 info@tianfuchem.com CHINA 20680 55
Mainchem Co., Ltd.
+86-0592-6210733
+86-0592-6210733 sales@mainchem.com CHINA 32457 55
career henan chemical co
+86-371-86658258
sales@coreychem.com CHINA 20516 58
Hubei Jusheng Technology Co.,Ltd.
86-188-71490254
peter@hubeijusheng.com CHINA 20094 58
Accela ChemBio Inc.
(+1)-858-699-3322
(+1)-858-876-1948 info@accelachem.com United States 12233 58
J & K SCIENTIFIC LTD. 400-666-7788 +86-10-82848833
+86-10-82849933 jkinfo@jkchemical.com;market6@jkchemical.com China 96815 76
Meryer (Shanghai) Chemical Technology Co., Ltd. +86-(0)21-61259100(Shanghai) +86-(0)755-86170099(ShenZhen) +86-(0)10-62670440(Beijing)
+86-(0)21-61259102(Shanghai) +86-(0)755-86170066(ShenZhen) +86-(0)10-88580358(Beijing) sh@meryer.com China 40277 62
INTATRADE GmbH +49 3493/605464
+49 3493/605470 sales@intatrade.de Germany 3580 66

View Lastest Price from Pyrazinamide manufacturers

Image Release date Product Price Min. Order Purity Supply Ability Manufacturer
2018-08-20 Pyrazinamide
98-96-4
US $1.00 / KG 1G 98% 100KG career henan chemical co
2018-08-20 Pyrazinamide
98-96-4
US $1.00 / KG 1KG 98% 100KG career henan chemical co

Pyrazinamide Spectrum


98-96-4(Pyrazinamide)Related Search:


  • LABOTEST-BB LT00233122
  • 2-PYRAZINECARBOXAMIDE
  • AKOS NCG1-0042
  • PYRAZINECARBOXAMIDE
  • PYRAZINOIC ACID AMIDE
  • PYRAZINE-2-CARBOXAMIDE
  • PYRAZINE-2-CARBOXYLIC ACID AMIDE
  • PYRAZINAMIDE
  • PZAD
  • TIMTEC-BB SBB004276
  • Pyrazinamide BP98,USP24,CP2000
  • Pyrazoinamide
  • PyrazinamideBp
  • Pyrazinamide>99%
  • PyrazinamidePyrazinamideBp/Usp/Ep
  • Pezetamid
  • Piraldina
  • Pirazinecarboxamide
  • PYRAZINAMIDE,USP
  • Pyrazine-2-carboxamide 97%
  • 2-(AMINOCARBONYL)-PYRAZINE(Pyrazinamide)
  • 2-Carbamylpyrazine
  • Aldinamid
  • Aldinamide
  • Eprazin
  • Farmizina
  • MK 56
  • mk56
  • NCI-C01785
  • Novamid
  • Pirazimida
  • Pirazinamid
  • Pyrafat
  • Pyrazinamid
  • Pyrazine Carboxylamide
  • Pyrazine-2-carboxamide(δ-modification)
  • Pyrazineamide
  • pyrazinecarboxylamide
  • Pyrazinecarboxylic acid amide
  • PZA
  • T 165
  • Tebrazid
  • Unipyranamide
  • Zinamide
  • PYRAZINAMIDE PYRAZINE-2-CARBOXYLIC ACID AMIDE
  • -
  • Amide
  • Heterocycles
  • Intermediates & Fine Chemicals
  • Pharmaceuticals
  • Pyrazines, Pyrimidines & Pyridazines
  • API
  • Pyrazinoic acid amide
  • TEBRAZID
  • Pyrazinamide, Pyrazinoic acid amide
  • Tisamid
  • Pyrazinamide (200 mg)
  • 2-Carbamoylpyrazine
Copyright 2017 © ChemicalBook. All rights reserved