- Raw materials
- Immunomodulators
- Immunosuppressants
- Azathioprine
Filters
Custom request?
Type
Production region
Qualifications
Country of origin
Azathioprine API Manufacturers & Suppliers
12 verified results
Commercial-scale Suppliers
All certificates
Employees: 25
All certificates
All certificates
All certificates
All certificates
All certificates
All certificates
All certificates
All certificates
All certificates
All certificates
All certificates
Total market transparency
Supplier trade data access
Buyer / supplier flow comparison
Azathioprine | CAS No: 446-86-6 | GMP-certified suppliers
A medication that provides immunosuppressive treatment for rheumatoid arthritis and prevention of renal transplant rejection in key global markets.
Therapeutic categories
Primary indications
- Azathioprine is indicated to treat rheumatoid arthritis and prevent renal transplant rejection
Product Snapshot
- Azathioprine is available in oral tablet and injectable powder formulations
- It is primarily used for immunosuppressive therapy in rheumatoid arthritis and prevention of renal transplant rejection
- The product is approved for use in key regulatory markets including the US, Canada, and the EU
Clinical Overview
Pharmacologically, azathioprine functions through multiple immunosuppressive mechanisms. Its active metabolites, notably 6-thioguanine nucleotides, inhibit de novo purine synthesis, suppressing DNA and RNA synthesis in rapidly proliferating cells such as B and T lymphocytes. This leads to decreased lymphocyte proliferation and function. Additionally, the metabolite 6-thioguanine triphosphate modulates the activation of rac1, a GTPase involved in T cell receptor signaling, which induces apoptosis of activated T cells. The exact pathways of immunosuppression are not fully elucidated but involve inhibition of key signaling cascades including mitogen-activated protein kinase and NF-kappaB.
Azathioprine has a long duration of action, necessitating daily dosing. Pharmacokinetically, it undergoes extensive hepatic metabolism, with metabolites excreted primarily through the renal route. It is a substrate for cytochrome P450 enzymes, including CYP1A2, and also interacts with drug transport proteins such as P-glycoprotein, which may influence its disposition.
The safety profile requires careful consideration due to its narrow therapeutic index and potential toxicities. Patients receiving azathioprine must be monitored for myelosuppression, increased susceptibility to infections, hepatotoxicity, and elevated risk of malignancies, particularly skin cancers and lymphomas. Genetic variability in thiopurine methyltransferase (TPMT) activity impacts azathioprine metabolism and toxic risk, underscoring the need for individualized dosing and monitoring.
From a pharmaceutical sourcing perspective, azathioprine is classified chemically as a diarylthioether and must meet strict purity criteria to ensure consistent potency and safety. Procurement of the API requires verification of manufacturing standards, regulatory compliance, and substantiation of impurity profiles, especially regarding thiopurine-related contaminants. Ensuring reliable supply chains and quality management systems is essential for maintaining therapeutic efficacy and patient safety.
Identification & chemistry
| Generic name | Azathioprine |
|---|---|
| Molecule type | Small molecule |
| CAS | 446-86-6 |
| UNII | MRK240IY2L |
| DrugBank ID | DB00993 |
Pharmacology
| Summary | Azathioprine is an immunosuppressive agent that inhibits purine synthesis and modulates Ras-related C3 botulinum toxin substrate 1 (rac1) activity, leading to T cell apoptosis. Its mechanism involves interference with B and T lymphocyte function and downstream signaling pathways including MAP kinase and NF-kappaB. It is primarily used to reduce immune responses in conditions such as rheumatoid arthritis and organ transplant rejection. |
|---|---|
| Mechanism of action | Azathioprine's mechanism of action is not entirely understood but it may be related to inhibition of purine synthesis, along with inhibition of B and T cells. 6-thioguanine triphosphate, a metabolite of azathioprine, modulates activation of rac1 when costimulated with CD28, inducing T cell apoptosis. This may be mediated through rac1's action on mitogen-activated protein kinase, NF-kappaB. |
| Pharmacodynamics | Azathioprine is an immunosuppressive agent which functions through modulation of rac1 to induce T cell apoptosis, as well as other unknown immunosuppressive functions. It has a long duration of action as it is given daily, and has a narrow therapeutic index. Patients should be counselled regarding the risk of malignancies of the skin and lymphomas. |
Targets
| Target | Organism | Actions |
|---|---|---|
| Ras-related C3 botulinum toxin substrate 1 | Humans | modulator |
ADME / PK
| Absorption | Oral azathioprine is well absorbed, with a T<sub>max</sub> of 1-2h. Further data regarding the absorption of azathioprine is not readily available. |
|---|---|
| Half-life | The half life of azathioprine is approximately 5 hours. |
| Protein binding | Azathioprine is 30% bound to proteins such as human serum albumin in circulation. |
| Metabolism | Azathioprine is converted to 6-mercaptopurine nonenzymatically. 6-mercaptopurine is then metabolized to 6-methylmercaptopurine by thiopurine methyltransferase, 6-thiouric acid by xanthine oxidase, or 6-thiosine-5'-monophosphate by hypoxanthine phosphoribosyltransferase. 6-thiosine-5'-monophosphate is metabolized to 6-methylthiosine-5'-monophosphate by thiopurine methyltransferase or 6-thioxanthylic acid by inosine monophosphate dehydrogenase. 6-thioxanthylic acid is metabolized by guanosine monophosphate synthetase to 6-thioguanine monophosphate, the first of the 6-thioguanine nucleotides. 6-thioguanine monophosphate is phosphorylated to produce the remaining 6-thioguanine nucleotides, 6-thioguanine diphosphate and 6-thioguanine triphosphate. |
| Route of elimination | Azathioprine and mercaptopurine are not detectable in urine after 8 hours. Further data regarding the route of elimination of azathioprine are not available. |
| Volume of distribution | Data regarding the volume of distribution of azathioprine is not readily available. |
| Clearance | Data regarding the clearance of azathioprine is not readily available. |
Formulation & handling
- Azathioprine is a small molecule drug available for both oral and intravenous administration, requiring formulation for tablets, suspensions, or injectable lyophilized powders.
- Formulations should consider the need for oral administration with food to reduce gastrointestinal irritation and improve tolerability.
- The solid form exhibits moderate water solubility and stability considerations should include protection from moisture for lyophilized injectable powders.
Regulatory status
| Lifecycle | The API is currently mature in the US, Canada, and EU markets, with patent protection expired or expiring shortly, allowing for generic competition and increased market availability. Ongoing regulatory approvals continue to influence its market penetration across these regions. |
|---|
| Markets | Canada, US, EU |
|---|
Supply Chain
| Supply chain summary | The manufacturing landscape for azathioprine includes multiple originator and generic manufacturers, reflecting a competitive supply environment. Branded and generic forms are present across major markets including the US, EU, and Canada, indicating broad global availability. Patent expiry has led to established generic competition, as evidenced by numerous manufacturers and repackagers operating in this space. |
|---|
Safety
| Toxicity | The oral LD<sub>50</sub> in mice is 2500mg/kg and in rats is 400mg/kg. Patients experiencing an overdose may present with bone marrow hypoplasia, bleeding, and infection, which may progress to death. Patients should be treated with supportive and symptomatic treatments. 8 hour hemodialysis may remove 45% of a dose from serum. |
|---|
- Oral LD50 values are 2500 mg/kg in mice and 400 mg/kg in rats, indicating species-specific acute toxicity
- Overdose may lead to bone marrow hypoplasia, bleeding, and increased risk of infection
- Hemodialysis can remove approximately 45% of serum drug after an 8-hour session
Azathioprine is a type of Immunosuppressants
Immunosuppressants are a vital subcategory of pharmaceutical active pharmaceutical ingredients (APIs) that play a crucial role in medical treatments. These substances are designed to suppress or weaken the immune system's response, making them invaluable in various therapeutic applications.
Immunosuppressants find extensive use in the management of autoimmune diseases, organ transplantation, and the prevention of rejection reactions. By modulating the immune system's activity, these APIs help control excessive immune responses that can lead to tissue damage and chronic inflammation.
There are different classes of immunosuppressants, including corticosteroids, calcineurin inhibitors, antimetabolites, and biologics. Each class targets specific immune pathways to achieve the desired therapeutic effect. Corticosteroids, for instance, are known for their potent anti-inflammatory properties, making them effective in managing conditions such as rheumatoid arthritis and asthma.
Calcineurin inhibitors like cyclosporine and tacrolimus act by inhibiting the activity of calcineurin, a protein involved in immune cell activation. These drugs are commonly used in organ transplantation to prevent the immune system from attacking the transplanted organ.
Antimetabolites interfere with DNA synthesis and cell proliferation, thereby dampening immune responses. They are often prescribed for conditions like psoriasis and rheumatoid arthritis.
Biologic immunosuppressants, such as monoclonal antibodies, target specific immune cells or molecules involved in the disease process. They have revolutionized the treatment of autoimmune diseases like rheumatoid arthritis, Crohn's disease, and psoriasis.
Immunosuppressants require careful administration and monitoring due to their potential side effects and interactions with other medications. Close collaboration between healthcare professionals, pharmacists, and patients is essential to ensure the safe and effective use of these APIs in various therapeutic settings.
Overall, immunosuppressants represent a critical category of pharmaceutical APIs that significantly contribute to improving patients' quality of life by controlling the immune system's activity and managing various autoimmune conditions and transplantation outcomes.
Azathioprine (Immunosuppressants), classified under Immunomodulators
Immunomodulators, a category of pharmaceutical active pharmaceutical ingredients (APIs), are substances that help regulate and modify the immune response of an individual. These compounds play a crucial role in treating various immune-related disorders and diseases. Immunomodulators work by either enhancing or suppressing the immune system, depending on the specific condition being treated.
Immunomodulators are used in the treatment of autoimmune disorders, such as rheumatoid arthritis, multiple sclerosis, and psoriasis. By suppressing the immune system, these APIs help reduce the overactive immune response associated with these conditions, thereby alleviating symptoms and preventing further damage to the body's tissues.
On the other hand, immunomodulators are also employed to boost the immune system in cases of immunodeficiency disorders. These APIs stimulate the immune response, enabling the body to better fight off infections and diseases. Additionally, immunomodulators are utilized in the prevention and treatment of organ transplant rejection, where they help modulate the immune system to accept the transplanted organ.
The development and production of immunomodulators require rigorous testing and quality control to ensure their safety and efficacy. Pharmaceutical companies carefully formulate these APIs into various dosage forms, including tablets, capsules, injections, and topical preparations, to cater to different patient needs.
In summary, immunomodulators form a vital category of pharmaceutical APIs that regulate and modify the immune system. With their ability to modulate immune responses, these compounds contribute significantly to the management and treatment of various immune-related disorders and diseases, improving the quality of life for many patients.
Azathioprine API manufacturers & distributors
Compare qualified Azathioprine API suppliers worldwide. We currently have 12 companies offering Azathioprine API, with manufacturing taking place in 6 different countries. Use the table below to review supplier type, countries of origin, certifications, product portfolio and GMP audit availability.
| Supplier | Type | Country | Product origin | Certifications | Portfolio |
|---|---|---|---|---|---|
| Fermion | Producer | Finland | Finland | BSE/TSE, CEP, CoA, GDP, GMP, JDMF, MSDS, USDMF | 29 products |
| Fine Chemicals | Producer | South Africa | South Africa | CEP, CoA, FDA, USDMF | 14 products |
| Global Pharma Tek | Distributor | India | India | BSE/TSE, CoA, FDA, GMP, ISO9001, MSDS | 484 products |
| Humble Healthcaare | Producer | India | India | CoA | 30 products |
| Kleem Pharmaceuticals | Producer | India | India | CoA | 22 products |
| Microbiologica | Producer | Brazil | Brazil | CEP, CoA | 1 products |
| P&H | Distributor | Netherlands | Finland | CoA | 1 products |
| Raks Pharma | Producer | India | India | CoA, USDMF | 58 products |
| Resolution Chemicals | Producer | United Kingdom | United Kingdom | CEP, CoA, USDMF | 1 products |
| Rpg Life Sciences | Producer | India | India | CEP, CoA, USDMF, WC | 13 products |
| Unnati Pharmaceuticals Pv... | Distributor | India | India | CoA | 70 products |
| Zhejiang Chengyi | Producer | China | China | CoA, USDMF, WC | 5 products |
When sending a request, specify which Azathioprine API quality you need: for example EP (Ph. Eur.), USP, JP, BP, or another pharmacopoeial standard, as well as the required grade (base, salt, micronised, specific purity, etc.).
Use the list above to find high-quality Azathioprine API suppliers. For example, you can select GMP, FDA or ISO certified suppliers. Visit our help page to learn more about sourcing APIs via Pharmaoffer.
