Isoniazid
- CAS No.
- 54-85-3
- Chemical Name:
- Isoniazid
- Synonyms
- ISONICOTINOHYDRAZIDE;INH;ISONIAZIDE;Nydrazid;PYRIDINE-4-CARBOHYDRAZIDE;ISONICOTINIC ACID HYDRAZIDE;HIA;Hyzyd;Rimifon;rifamate
- CBNumber:
- CB5102053
- Molecular Formula:
- C6H7N3O
- Molecular Weight:
- 137.14
- MOL File:
- 54-85-3.mol
- MSDS File:
- SDS
- Modify Date:
- 2024/7/26 15:15:06
| Melting point | 171-173 °C (lit.) |
|---|---|
| Boiling point | 251.97°C (rough estimate) |
| Density | 1.2620 (rough estimate) |
| refractive index | 1.6910 (estimate) |
| Flash point | >250°C |
| storage temp. | 2-8°C |
| solubility | 125g/l |
| pka | pKa 2.00/3.60/10.8(H2O) (Uncertain) |
| form | Crystals or Crystalline Powder |
| color | White or colorless |
| Odor | Odorless |
| PH Range | 5.5 - 6.5 at 10 g/l at 25 °C |
| PH | 6-8 (50g/l, H2O, 20℃) |
| Water Solubility | 14 g/100 mL (25 ºC) |
| Sensitive | Air Sensitive |
| Merck | 14,5186 |
| BRN | 119374 |
| BCS Class | 1,3 |
| Stability | Stability Stable, but may be air or light sensitive. Combustible. Incompatible with strong oxidizing agents, chloral, aldehydes, iodine, ferric salts, hypochlorites. |
| InChIKey | QRXWMOHMRWLFEY-UHFFFAOYSA-N |
| CAS DataBase Reference | 54-85-3(CAS DataBase Reference) |
| IARC | 3 (Vol. 4, Sup 7) 1987 |
| NIST Chemistry Reference | Isoniazid(54-85-3) |
| EPA Substance Registry System | Isoniazid (54-85-3) |
SAFETY
Risk and Safety Statements
| Symbol(GHS) |  GHS07 |
|||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Signal word | Warning | |||||||||
| Hazard statements | H302-H315 | |||||||||
| Precautionary statements | P264-P270-P280-P301+P312-P302+P352-P332+P313 | |||||||||
| Hazard Codes | Xn | |||||||||
| Risk Statements | 22-38-40-36/37/38 | |||||||||
| Safety Statements | 37-36/37/39-26 | |||||||||
| RIDADR | 2811 | |||||||||
| WGK Germany | 3 | |||||||||
| RTECS | NS1751850 | |||||||||
| TSCA | Yes | |||||||||
| PackingGroup | III | |||||||||
| HS Code | 29333999 | |||||||||
| Toxicity | LD50 in mice (mg/kg): 151 i.p., 149 i.v. (Jenney, Pfeiffer) | |||||||||
| NFPA 704 |
|
Isoniazid price More Price(13)
| Manufacturer | Product number | Product description | CAS number | Packaging | Price | Updated | Buy |
|---|---|---|---|---|---|---|---|
| Sigma-Aldrich(India) | I3377 | Isoniazid analytical standard, ≥99% (TLC) | 54-85-3 | 5G | ₹2381.5 | 2022-06-14 | Buy |
| Sigma-Aldrich(India) | I3377 | Isoniazid analytical standard, ≥99% (TLC) | 54-85-3 | 50G | ₹9212.08 | 2022-06-14 | Buy |
| Sigma-Aldrich(India) | PHR1932 | Isoniazid Pharmaceutical Secondary Standard; Certified Reference Material | 54-85-3 | 500MG | ₹15826.15 | 2022-06-14 | Buy |
| Sigma-Aldrich(India) | I3377 | Isoniazid analytical standard, ≥99% (TLC) | 54-85-3 | 250G | ₹18283.43 | 2022-06-14 | Buy |
| TCI Chemicals (India) | I0138 | Isonicotinic Acid Hydrazide | 54-85-3 | 25G | ₹1600 | 2022-05-26 | Buy |
Isoniazid Chemical Properties,Uses,Production
Description
Isoniazid, the hydrazide of isonicotinic acid was introduced into medical practice for treating tuberculosis in 1953. Isoniazid exhibits bactericidal action on Mycobacterium tuberculosis. It inhibits the synthesis of mycolic acid, an important component of the cell
membrane of mycobacteria. Mycolic acid is specific only to mycobacteria, and it is the
cause of the selective toxicity of the drug with respect to these microorganisms.
Mutants that are resistant to isoniazid are rarely seen in nature, and in a spontaneously
growing population of tuberculous bacillus there is approximately one mutant in every
105
–106 organisms. Large populations of microorganisms of the order 109
–1010 bacilli in
the pulmonary cavities contain a significant number of resistant mutants. If only isoniazid
is taken during treatment, an increased number of mutants will be observed and they will
eventually become the dominant phenotype. The transformation from sensitive to nonsensitive microorganisms during treatment is called secondary or acquired resistance, which
can originate over the course of a few weeks. Isoniazid is the most important drug for treating pulmonary and nonpulmonary forms of tuberculosis. It is active against both intracellular and extracellular organisms. In order to prevent secondary resistance, isoniazid
should be used with other effective drugs (usually rifampin). Synonyms of this drug are
tubazid, andrazide, niazid, piridizin, and many others.
Chemical Properties
white crystalline powder
Uses
Isoniazid is an antimicrobial used for the prevention of tuberculosis infection or used concurrently with another agent for the treatment of tuberculosis infection. Rifampin, pyrazinamide, or both of these agents are commonly used with isoniazid. Isoniazid is the only Food and Drug Administration approved drug to treat latent tuberculosis in order to prevent it from becoming active.
Indications
Isoniazid (isonicotinic acid hydrazide, or INH) is the most active drug for the treatment of tuberculosis caused by susceptible strains. It is a synthetic agent with a structural similarity to that of pyridoxine.
Definition
ChEBI: A carbohydrazide obtained by formal condensation between pyridine-4-carboxylic acid and hydrazine.
Biological Functions
Its action is bactericidal against replicating organisms, but it appears to be only bacteriostatic at best against semidormant and dormant populations. After treatment with INH, M . tuberculosis loses its acid fastness, which may be interpreted as indicating that the drug interferes with cell wall development.
Antimicrobial activity
Susceptibility to isoniazid is virtually restricted to the M. tuberculosis complex (MIC 0.01–0.2 mg/L). It is highly bactericidal against actively replicating M. tuberculosis. Other mycobacteria are resistant, except for some strains of M. xenopi (MIC 0.2 mg/L) and a few strains of M. kansasii (MIC 1 mg/L).
Acquired resistance
Mutations in the katG gene, the inhA gene or its promoter
region, and in the intergenic region of the oxyR–ahpC locus
confer resistance to isoniazid. The relative
proportions of such mutations vary geographically and
are related to the distribution of the various lineages or superfamilies
of M. tuberculosis.
Isoniazid resistance is the commonest form of drug resistance
worldwide and the great majority of strains resistant to
another agent are also resistant to isoniazid.
General Description
Odorless colorless or white crystals or white crystalline powder. Taste is slightly sweet at first and then bitter. pH (1% aqueous solution) 5.5-6.5. pH (5% aqueous solution) 6-8.
Air & Water Reactions
Sensitive to air and light. Absorbs insignificant amounts of moisture at 77°F at relative humidities up to approximately 90%. Water soluble. Dust can be explosive when suspended in air at specific concentrations.
Reactivity Profile
Isoniazid is incompatible with chloral, aldehydes, iodine, hypochlorites and ferric salts. Isoniazid is also incompatible with oxidizers. Isoniazid may react with sugars and ketones. Isoniazid can react as a weak acid or a weak base. Isoniazid can be decomposed by oxidative and reductive reactions.
Fire Hazard
Isoniazid is combustible.
Pharmaceutical Applications
One of a number of nicotinamide analogs found to have antituberculosis activity, following the observation that nicotinamide inhibited the replication of M. tuberculosis. It is soluble in water. The dry powder is stable if protected from light. It is a prodrug requiring oxidative activation by KatG, a mycobacterial catalase–peroxidase enzyme.
Mechanism of action
Isoniazid is active against susceptible bacteria only when they are undergoing cell division. Susceptible bacteria may continue to undergo one or two divisions before multiplication is arrested. Isoniazid can inhibit the synthesis of mycolic acids, which are essential components of mycobacterial cell walls.The mycobacterial enzyme catalase– peroxidase KatG activates the administered isoniazid to its biologically active form.The target sites for the activated isoniazid action are acyl carrier protein AcpM and Kas A, a β-ketoaceyl carrier protein synthetase that blocks mycolic acid synthesis. Isoniazid exerts its lethal effects at the target sites by forming covalent complexes.
Pharmacology
Isoniazid is water soluble and is well absorbed when
administered either orally or parenterally. Oral absorption
is decreased by concurrent administration of
aluminum-containing antacids.
Isoniazid does not bind to serum proteins; it diffuses
readily into all body fluids and cells, including the
caseous tuberculous lesions. The drug is detectable in
significant quantities in pleural and ascitic fluids, as well
as in saliva and skin. The concentrations in the central
nervous system (CNS) and cerebrospinal fluid are generally
about 20% of plasma levels but may reach close
to 100% in the presence of meningeal inflammation.
Isoniazid is acetylated to acetyl isoniazid by N-acetyltransferase,
an enzyme in liver, bowel, and kidney.
Individuals who are genetically rapid acetylators will have
a higher ratio of acetyl isoniazid to isoniazid than will slow
acetylators. Rapid acetylators were once thought to be
more prone to hepatotoxicity, but this is not proved. The
slow or rapid acetylation of isoniazid is rarely important
clinically, although slow inactivators tend to develop peripheral
neuropathy more readily. Metabolites of isoniazid
and small amounts of unaltered drug are excreted in
the urine within 24 hours of administration.
Pharmacokinetics
Oral absorption: >95%
Cmax 300 mg oral: 3–5 mg/L after 1–2 h
Plasma half-life: 0.5–1.5 h (rapid acetylators)
:
2–4 h (slow acetylators)
Volume of distribution: 0.6–0.8 L/kg
Plasma protein binding: Very low
Absorption and distribution
Isoniazid is almost completely absorbed from the gut and is well distributed. Absorption is impaired by aluminum hydroxide. Therapeutic concentrations are achieved in sputum and CSF. It crosses the placenta and is found in breast milk.
Metabolism
Isoniazid is extensively metabolized to a variety of pharmacologically inactive derivatives, predominantly by acetylation. As a result of genetic polymorphism, patients are divisible into rapid and slow acetylators. About 50% of Caucasians and Blacks, but 80–90% of Chinese and Japanese, are rapid acetylators. Acetylation status does not affect the efficacy of daily administered therapy. The rate of acetylation is reduced in chronic renal failure.
Excretion
Nearly all the dose is excreted in the urine within 24 h, as unchanged drug and metabolic products.
Clinical Use
Isonicotinic acid hydrazide, isonicotinyl hydrazide, or INH(Nydrazid) occurs as a nearly colorless crystalline solid thatis very soluble in water. It is prepared by reacting the methylester of isonicotinic acid with hydrazine.
Isoniazid is a remarkably effective agent and continuesto be one of the primary drugs (along with rifampin, pyrazinamide,and ethambutol) for the treatment of tuberculosis.It is not, however, uniformly effective against all formsof the disease. The frequent emergence of strains of the tuberclebacillus resistant to isoniazid during therapy wasseen as the major shortcoming of the drug. This problemhas been largely, but not entirely, overcome with the use ofcombinations.
The activity of isoniazid is manifested on the growing tuberclebacilli and not on resting forms. Its action, which isconsidered bactericidal, is to cause the bacilli to lose lipidcontent by a mechanism that has not been fully elucidated.The most generally accepted theory suggests that the principaleffect of isoniazid is to inhibit the synthesis of mycolicacids, high–molecular-weight, branched β-hydroxyfatty acids that constitute important components of the cellwalls of mycobacteria.
Side effects
The incidence and severity of adverse reactions to isoniazid are related to dosage and duration of therapy. Isoniazid-induced hepatitis and peripheral neuropathy are two major untoward effects.
Environmental Fate
Isoniazid is a colorless, odorless, white crystalline powder that is slowly oxidized by exposure to air. It undergoes degradation upon prolonged exposure to light. Isoniazid has a solubility of 1 g per 8 ml water, 1 g per 50 ml ethanol, and it is slightly soluble in chloroform and very slightly soluble in ether. A 10% solution of isoniazid has a pH of 6.0–8.0.
Metabolism
Isoniazid is extensively metabolized to inactive metabolites. The major metabolite is N-acetylisoniazid. The enzyme responsible for acetylation, cytosolic N-acetyltransferase, is produced under genetic control in an inherited autosomal fashion. Individuals who possess high concentrations of the enzyme are referred to as rapid acetylators, whereas those with low concentrations are slow acetylators. This may result in a need to adjust the dosage for fast acetylators. The N-acetyltransferase is located primarily in the liver and small intestine. Other metabolites include isonicotinic acid, which is found in the urine as a glycine conjugate, and hydrazine. Isonicotinic acid also may result from hydrolysis of acetylisoniazid, but in this case, the second product of hydrolysis is acetylhydrazine. Acetylhydrazine is acetylated by N-acetyltransferase to the inactive diacetyl product. This reaction occurs more rapidly in rapid acetylators. The formation of acetylhydrazine is significant in that this compound has been associated with the hepatotoxicity, which may occur during INH therapy.
Purification Methods
Crystallise isoniazide from 95% EtOH and dry it in a vacuum. [Beilstein 22 III/IV 545, 22/2 V 219.]
Precautions
High isoniazid plasma levels inhibit phenytoin metabolismand potentiate phenytoin toxicity when the twodrugs are coadministered. The serum concentrations ofphenytoin should be monitored, and the dose should beadjusted if necessary.
Isoniazid Preparation Products And Raw materials
Raw materials
1of2
chevron_rightPreparation Products
1of2
chevron_right| Supplier | Tel | Country | ProdList | Advantage | Inquiry |
|---|---|---|---|---|---|
| BIOCHEMICAL & SYNTHETIC PRODUCTS PVT. LT., | +91-91-8421973722 +91-9869455944 | Telangana, India | 31 | 58 | Inquiry |
| Island Veer Chemie Pvt Ltd | +917093280665 | Telangana, India | 32 | 58 | Inquiry |
| SYNOVA CHEMICALS | +91-9920741772 +91-9920741772 | Mumbai, India | 428 | 58 | Inquiry |
| JSK Chemicals | +919879767970 | Gujarat, India | 3756 | 58 | Inquiry |
| Anuh Pharma Ltd (SK GROUP) | +912266227575 | Maharashtra, India | 38 | 58 | Inquiry |
| Calyx Chemicals and Pharmaceuticals Ltd | +919819317220 | Mumbai, India | 15 | 58 | Inquiry |
| ALS INDIA LIFE SCIENCES | +91-8977036379 +91-8977036379 | Hyderabad, India | 1879 | 58 | Inquiry |
| Amsal Chem Private Limited | +91-2222050500 +91-2222050500 | Maharashtra, India | 15 | 58 | Inquiry |
| Ralington Pharma | +91-7948911722 +91-9687771722 | Gujarat, India | 1350 | 58 | Inquiry |
| Alfa Omega Pharma | +91-8050045945 +91-9972665399 | Maharashtra, India | 126 | 58 | Inquiry |
Related articles
- Mechanism of action of Isoniazid
- Isoniazid, isonicotinic acid hydrazide (INAH or INH), was discovered independently in 1952 at both Squibb and Roche Laboratori....
- Mar 25，2022
54-85-3(Isoniazid)Related Search:
1of4
chevron_right