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 Azathioprine Sodium

azathioprine sodium is the sodium salt form of azathioprine, a pro-drug of purine analogue with immunosuppressive activity. Azathioprine is converted in vivo to its active metabolite 6-mercaptopurine (6-MP), which substitutes for the normal nucleoside and mistakenly gets incorporated into DNA sequences. This leads to inhibition of DNA, RNA, and protein synthesis. As a result, cell proliferation may be inhibited, particularly in lymphocytes and leukocytes. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).

Azathioprine is used in organ transplantation and autoimmune disease. Some of the autoimmune diseases are rheumatoid arthritis, pemphigus, Inflammatory Bowel Disease (such as Crohn's disease and Ulcerative Colitis), multiple sclerosis, autoimmune hepatitis, atopic dermatitis, Myasthenia Gravis and restrictive lung disease. Azathioprine interferes with the synthesis of purines (adenine and guanine), which is required for DNA synthesis. Fast-growing cells, including T-cells and B-cells, are particularly affected by the inhibition of purine synthesis. It is a pro-drug, converted in the body to the active metabolites 6-mercaptopurine (6-MP) and 6-thioinosinic acid. Azathioprine is produced by a number of generic manufacturers and as branded names (Azasan by Salix in the U.S., Imuran by GlaxoSmithKline in Canada and the U.S., Australia and UK, Azamun in Finland and Imurel in Scandinavia and France).

According to http://en.wikipedia.org/wiki/Azathioprine, Azathioprine was first introduced into clinical practice by Sir Roy Calne, the British pioneer in transplantation. Following the work done by Sir Peter Medawar in discovering the immunological basis of rejection of transplanted tissues and organs, Calne introduced 6-mercaptopurine as an experimental immunosuppressant for kidney transplants cardiac transplantation. When azathioprine was discovered, he then introduced it as a less toxic replacement for 6-mercaptopurine. For many years, dual therapy with azathioprine and steroids was the standard anti-rejection regime, until cyclosporine was introduced into clinical practice (also by Calne) in 1978.

DRUG DESCRIPTION

AZASAN®, an immunosuppressive antimetabolite, is available in tablet form for oral administration. Each scored tablet contains 75 mg or 100 mg azathioprine and the inactive ingredients lactose monohydrate, pregelatinized starch, povidone, corn starch, magnesium stearate, and stearic acid. It is an imidazolyl derivative of 6-mercaptopurine and many of its biological effects are similar to those of the parent compound. Azathioprine is insoluble in water, but may be dissolved with addition of one molar equivalent of alkali. The sodium salt of azathioprine is sufficiently soluble to make a 10 mg/mL water solution which is stable for 24 hours at 59° to 77°F (15° to 25°C). Azathioprine is stable in solution at neutral or acid pH but hydrolysis to mercaptopurine occurs in excess sodium hydroxide (0.1N), especially on warming. Conversion to mercaptopurine also occurs in the presence of sulfhydryl compounds such as cysteine, glutathione, and hydrogen sulfide.

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