What Is Zidovudine?
Zidovudine is an antiviral drug for the treatment of patients with AIDS or AIDS-related syndromes and immunodeficiency virus (HIV) infections. On March 19, 1987, the US Food and Drug Administration approved the drug for marketing. Zidovudine is the first anti-AIDS drug in the world to be approved by the US FDA. Because of its precise effect, it has become the most basic combination of "cocktail" therapy. This product is an antiviral drug and has high activity against retroviruses including human immunodeficiency virus (HIV) in vitro. Phosphorylation of zidovudine triphosphate by the cell thymidine kinase in virus-infected cells selectively inhibits HIV reverse enzymes, leading to the termination of HIV chain synthesis and preventing HIV replication.
Zidovudine
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- Combined with the virus's DNA polymerase, it stops the growth of the DNA strand, thereby suppressing the virus's replication. It has little effect on human -DNA polymerase without inhibiting human cell proliferation.
- Oral absorption is rapid. After taking capsules, after first pass metabolism, the bioavailability is 52% to 75%. After 2.5 mg / kg intravenous infusion for 1 hour or 5 mg / kg orally, the blood concentration can reach 4-6 mol / L (1.1-1.6 mg / L); 4 hours after administration, the cerebrospinal fluid concentration can reach 50 60%; VD = 1.6L / kg; protein binding rate is about 34 38%; the product is mainly glucuronidated into the inactive GAZT in the liver; oral t1 / 2 for 1 hour; intravenous drip t1 / 2 for 1.1 hours . About 14% of the drugs passed
- Alias: Azide deoxythymidine, azidothymidine, zidovudine, azidothymidine
- Dangerous goods mark Xn-Harmful hazardous goods danger category code R40-Limited evidence of a carcinogenic effect. A few reports have carcinogenic consequences.
- safety instructions:
- S36 / 37 / 39-Wear suitable protective clothing, gloves and eye / face protection.
- Wear appropriate protective clothing, gloves and goggles or masks.
- S45-In case of accident or if you feel unwell, seek medical advice immediately (show the label whenever possible.)
- In case of accident or if you feel unwell, seek medical advice immediately (show the label if possible).
- WGK Germany 3
- RTECS number XP2072000
- F 10
- Hazard Note Harmful
- It is reported in the literature that pharmacokinetic studies have been performed in 22 male HIV-infected patients. Zidovudine can be quickly absorbed after oral administration, and the blood concentration reaches a peak within 0.5 to 1.5 hours after administration; The drug dose is 2 mg / kg to 10 mg / kg every 4 hours, and the drug dose is not related to pharmacokinetic parameters; the elimination half-life of zidovudine is about 1 hour (0.78 to 1.93 hours). Zidovudine can be quickly converted to 3'-azido-3'-deoxy-5'-oD-GZDV, which has a half-life of 1 hour (0.61 to 1.73). After oral administration, zidovudine is recovered from urine Ding and GZDV accounted for 14% and 74% of the total dose, respectively, and the average urine recovery was 90% (63% to 95%), indicating a higher recovery rate. However, due to the first pass effect, the average oral bioavailability of the product was 65% (52% to 95%).
- Adults: If used in combination with other antiretroviral drugs, the recommended dose of this product is 600 mg daily in divided doses; if this product is used alone, 500 mg / day or 600 mg / day is recommended to be taken in divided portions (every 4 times when awake 100mg per hour).
- Children: The recommended dosage for children from 3 months to 12 years is 180 mg / m2 every 6 hours and should not exceed 200 mg / m2 every 6 hours. Dosing for newborns: 12 to 6 hours after birth
- As the disease progresses, adverse reactions increase, and patients should be carefully monitored, especially as the disease progresses.
- Myelosuppression
- This product gives poor bone marrow function. People with granulocytes <1000 cells / mm3 or hemoglobin <9.5g / dl should be careful. For patients with severe AIDS, anemia and neutropenia are also the most obvious adverse reactions. Whole blood cell anemia associated with the use of this product has been reported, and most people can recover after discontinuation of the drug. However, when the product is administered alone or in combination, it is found that anemia is obvious, and it is necessary to adjust the dose, stop the drug and / or transfusion. Blood cell counts should be performed frequently in patients with progressive HIV given this product. Blood cells should be counted intermittently in patients with early or asymptomatic HIV infection. If anemia or neutrophil deficiency occurs, dose adjustments should be made.
- Myopathy
- Cardiomyopathy and myocarditis similar to HIV disease are related to long-term use of the product.
- Lactic acidosis / severe hepatic steatosis
- Occasional fatal lactic acidosis and its occurrence have been reported using nucleoside analog antiretrovirals
- 1, combined with Ganciclovir (Ganciclovir): in some advanced patients can increase blood toxicity. If these patients require a combination of drugs, the dose should be reduced or one or both of these drugs should be discontinued to reduce liver toxicity. Patients in combination should often perform hemoglobin, hematocrit,
- Both adult and pediatric use of doses exceeding 50 g have been reported, and neither has been fatal. These reported events were spontaneous or induced nausea and vomiting. Blood changes are transient and not severe, and some patients have nonspecific CNS symptoms such as headache, dizziness, drowsiness, fatigue, and unconsciousness. A 35-year-old man took 36g of the product at one time, and seizures occurred after 3 hours. Since no other cause was found, it may be caused by drugs. All patients recovered without sequelae. Hemodialysis or peritoneal dialysis has no effect on excretion of this product, but its metabolite GZDV excretion increases.
- Zidovudine (AZT), an anti-AIDS drug that has been around for a long time but has not been promoted, has continued to work hard, and has also achieved good results, which will make everyone impressed. According to HealthNet data, in July 2005, Zidov was still a heavyweight product, and the price of its raw materials rose to more than 400 US dollars per kilogram.
- Zidovudine was first synthesized in 1964. After continuous screening of compounds by scientists, it was developed and marketed by Wellcome in the United Kingdom. It was approved by the US FDA in March 1987. It was used for the first time in the prevention and treatment of HIV / AIDS. Named "Ritutovir", it has been used in clinical practice in nearly a hundred countries in the 20th century, and has been included in the 1998 edition of the British Pharmacopoeia and the 2000 edition of the United States Pharmacopoeia. So far the cumulative sales revenue has reached 4 billion US dollars. It is also the first of the 17 AIDS drugs approved by the FDA in 1987-1999.
- After the end of the administrative protection period of Zidovudine capsules in China in December 2001, the Northeast Pharmaceutical General Factory obtained a new drug certificate and production approval issued by the SFDA in August 2002 under the trade name "gram".
- As governments of various countries give green lights to AIDS medicine and strictly control the prices of such medicines, manufacturers will naturally not waste time and energy on a product that does not have much profitability. However, with the large increase in the incidence of diseases in the world, especially in developing countries, the huge demand still makes companies interested in developing and paying attention to these varieties.
- China's major domestic manufacturers include Northeast Pharmaceutical General Factory, Shandong Phoenix Pharmaceutical Co., Ltd., Hangzhou Keben Chemical Co., Ltd., Xiamen Mike Pharmaceutical Group, Anhui Baker Pharmaceuticals, etc., among which Anhui Baker Pharmaceuticals has internationally leading chiral compounds Synthetic technology, after 2002, several anti-AIDS drugs have been put into production, including zidovudine, lamivudine and stavudine.
- Due to the small amount of zidovudine, there are very few domestic manufacturers in China, but due to the strong demand for the AIDS drug market, there is still a shortage of supply and demand. Most manufacturers have no stock and orders have been scheduled to the second half of the year. From this perspective, there is still a considerable vacancy in this market.