| Outline |
Mizoribine is a kind of imidazole nucleoside isolated from the culture medium of ascomycetes M-2166 separated from the soil by Japanese scholars Asahi Kasei, being the metabolite which inhibiting the purine synthesis pathway of nucleic acid, mainly being used for inhibiting the rejection reaction before or after renal transplantation and also used for liver transplantation and autoimmune diseases.
Mizoribine, as a kind of immunosuppressant, its immunosuppressive effects may be related to its inhibition of purine nucleotide synthesis and increased transcriptional activity of the glucocorticoid receptor. It has been applied at Japanese clinical renal transplantation since December 1991. Many Japanese clinical transplant centers have applied mizoribine as the routine immunization inhibitory drug after kidney transplantation. In recent year, China has also applied kidney transplant anti-rejection drugs for clinical purpose. Mizoribine, compared with similar drugs azathioprine, has a low liver toxicity and bone marrow suppression effect with its main adverse reaction being the gastrointestinal reactions, blood disorders and allergic symptoms, and occasionally bone marrow suppression and acute renal failure. |
| Pharmacological effects |
This product is imidazole nucleoside anti-metabolite drug. Mizoribine, as a kind of pro-drugs, needs to undergo intracellular phosphorylation before taking effect. Its mechanism of immune suppression is mainly through inhibition of inosine monophosphate dehydrogenase (IMPDH) and guanosine monophosphate synthetase (GMP), and reducing the synthesis of guanylate as well as the synthesis of RNA, DNA, thereby inhibiting the proliferation of lymphocyte and the production of antibody, prolonging the survival time after organ transplantation, preventing the cell to be transferred from G1 to S phase. Because lymphocyte is not capable of synthesizing purine via salvage pathway, this product is able to selectively inhibit its activation. In addition, the product can interfere with the expression of cytokine receptors and antagonize the activation of lymphocyte mediated by cytokine. This product has a milder myelosuppression effect compared with azathioprine. The bioavailability of oral administration is relative low with large differences in individuals. After oral administration, the average time of plasma concentration for reaching peak is about 3 to 4 hours. This product is widely distributed in each body tissue with a higher concentration than that in the blood and with the highest concentration in the kidney and stomach. It is not easy to penetrate through the blood-brain barrier, but can penetrate through the placental barrier with a small amount shifting to the breast milk. It is mainly excreted through renal in its prototype with the elimination half-life being 2 to 5 hours.
The above information is edited by the Chemicalbook of Dai Xiongfeng. |
| Pharmacodynamics |
This product is able to inhibit the gastric transplant rejection with pharmacological effect of specifically inhibiting the proliferation of lymphocyte, and blocking the embryo-like conversion reaction induced by various kinds of mitogenic factors induced embryo-like conversion reaction, being able to extend the life of transplanted organs. It can inhibit the biosynthesis of nucleic acid through antagonizing the purine synthesis process from the pathway of inosine monophosphate to guanosine acid pathway without penetrating the nucleic acid polymer. |
| Side effects |
Mizoribine has bone marrow suppression effects such as causing reduction of white blood cells, platelets, and red blood cells. Occasionally there may also be liver damage, elevated blood urea nitrogen, gastrointestinal bleeding, allergies, fever, hair loss, lung infections, glossitis, and stomatitis. There are also loss of appetite, nausea, vomiting, diarrhea, and abdominal swelling feeling. |
| Precautions |
1. Patients allergic to this drug as well as with their white blood cell count being lower than 3 × 109/L, as well as pregnant women, lactating women should be disabled. Patients of bone marrow suppression, accompanied postoperative bacterial or viral infections, bleeding tendency, liver and kidney dysfunction should be used with caution.
2. The safety of children, women of childbearing age for using this drug has not been established.
3. We should pay close attention to the treatment of bleeding and infections during the treatment period. Moreover, we should perform regular investigation on the thermograms and liver and kidney function and discontinue or adjust the dose according to the medication condition. |
| Category |
toxic substances |
| Toxicity grading |
poisoning |
| Acute toxicity |
oral-rat LD50: 3100 mg/kg; intraperitoneal-Mouse LD50: 5000 mg/kg |
| Flammability and hazard properties |
Thermal decomposition can discharge toxic nitrogen oxides gases |
| Storage characteristics |
Treasury: ventilation, cool, dry |
| Extinguishing media |
Water, foam, sand, carbon dioxide, dry powder |
| Chemical Properties |
Crystalline Solid |
| Uses |
Nucleoside antibiotic with cytotoxic and immunosuppressive activity |
China
