What Is Adefovir?

Adefovir can be incorporated into a viral DNA strand competitively with adenylate. As a terminator of the DNA strand, it inhibits DNA polymerase and terminates the synthesis of the DNA strand. As a result, virus replication is inhibited and endogenous -interference can be induced It can increase the vitality of natural killer cells (NK) and stimulate the body's immune response, and has a strong anti-HIV, HBV and herpes virus effects.

Drug Name: Adefovir
Alias: Agandin, Dedin
Foreign name: Adefovir
Main indications: Chronic hepatitis B

Dosage: Adults 10 mg once daily
Adverse reactions: Fatigue, headache, abdominal pain, nausea, flatulence, diarrhea, etc.
Main medication contraindications: Caution for pregnant women
Dosage form: Piece / box

Adefovir compounds

Adefovir Basic Information

Chinese name: adefovir

Chinese alias: adefovir; 9- (2-phosphonomethoxyethyl) adenine; afovir; 9- (2-phosphonomethoxyethyl) adenine (PMEA);

English name: Adefovir

English alias: gs0393; ((2- (6-Amino-9H-purin-9-yl) ethoxy) methyl) phosphonic acid; PMEA;

CAS number: 106941-25-7

Molecular formula: C ₈ H ₁₂ N ₅ O ₄ P

Molecular weight: 273.18600

Exact mass: 273.06300

PSA: 146.19000

LogP: 0.14150

Adefovir physical and chemical properties

Appearance and properties: white to off-white powder

Density: 1.88

Melting point:> 260 ° C

Boiling point: 632.5ºCat 760 mmHg

Flash point: 336.3ºC

Adefovir safety information

Symbol: GHS06

Signal Word: Danger

Hazard statement: H301

Cautionary statement: P301 + P310

Packing level: III

Danger category: 8

Customs code: 2933990090

Dangerous Goods Transport Code: UN 2585 8 / PG 3

WGK Germany: 2

Danger category code: R36 / 37/38

Safety instructions: S26

Dangerous goods mark: Xi ^[1]

Adefovir production method

Isopropanol, pyridine and petroleum ether are mixed, and a petroleum ether solution of phosphorus trichloride is added dropwise under cooling. After the reaction, the filter cake is washed with petroleum ether. The filtrates are combined, concentrated under reduced pressure, and distilled to obtain triisophosphonic acid. Propyl ester. The ester was added dropwise to 1-chloro-2-chloromethoxyethane and reacted under reduced pressure to obtain 2-chloroethoxymethylphosphonic acid diisopropyl ester. Adenine was suspended in dimethylformamide, potassium carbonate was added, and 2-isochloroethoxymethylphosphonic acid diisopropyl ester was added dropwise to the reaction, filtered, concentrated under reduced pressure, and acetonitrile was recrystallized to obtain 9- (2-di Isopropoxyphosphonomethoxyethyl) adenine. Suspend the adenine in acetonitrile, add sodium iodide and trimethylchlorosilane, react under reflux, concentrate under reduced pressure, add water, adjust the pH to 7 with ammonia, adjust the pH to 4 with acetic acid, filter, and recrystallize with water Adefovir. Adefovir was suspended in dimethylformamide, and triethylamine, N, N-dicyclohexyl-4-morpholinamidine and chloromethyl pivalate were added to the reaction, followed by filtration, concentration, toluene extraction, Adifovir distil is obtained by evaporation.

Adefovir uses

It is used as an antiviral drug for the treatment of chronic hepatitis B, and also as an intermediate of adefovir (antihepatitis C drug) ^[1] .

Adefovir clinical trial

Adefovir is an adenine nucleoside analog. Adefovir dipivoxil is an oral preparation of adefovir. In the treatment of chronic hepatitis B, the dose is 10% to 25% of HIV infection, and the toxic and side effects are small.

Xiong et al. Confirmed in vitro experiments that HBV resistant to lamivudine is still sensitive to adefovir. Tsiang et al. Studied the kinetics of HBV biological clearance during adefovir treatment. Adefovir was found to be used to treat hepatitis B and HBV clearance was found to be bipolar. The first phase is the rapid clearance period. The half-life of HBV in plasma is 1.1 ± 0.3 d, and the free virus is cleared by 48% every day. Phase 2 is the slow clearance period, and the half-life of HBV is 18 ± 7 d, which reflects the disappearance of infected liver cells.

Gilson et al. Reported the results of a / clinical study of adefovir dipivoxil in the treatment of chronic HBV infection. The study was a double-blind, placebo-controlled method. Twenty patients joined the study, three of whom had HBV and HIV co-infection. All patients had positive HBsAg, HBeAg, and HBV DNA, and had abnormal ALT. Treated with adefovir dipivoxil 125 mg / d or placebo for 28 days. After treatment, the HBV DNA level of all patients receiving adefovir decreased to less than 1 log10, while the control group increased by 0.01 log10 pg / ml. After stopping the drug, the DNA returned to the level before treatment. One patient had a transient negative conversion of HBeAg, and another patient developed HBeAg and seroconversion 12 weeks after the end of treatment. Elevated ALT may occur in some patients during treatment.

Clinical trials have proven that adefovir is effective in treating lamivudine and famciclovir-resistant chronic hepatitis B patients. Heathcote et al. Used adefovir 5 mg / d, 30 mg / d, and 60 mg / d for 12 weeks to treat chronic hepatitis B patients. At the end of treatment, blood HBV DNA levels decreased by 4 log 10. HBeAg only turned negative in patients with elevated ALT, and was highest in the 30m / d dose group, reaching 27%. At the same time, it was found that patients could develop ALT elevation during the course of adefovir treatment. Further research has shown that patients with elevated ALT have increased specific Th cell activity. The reason for this increase in Th cell activity is whether adefovir has the effect of activating cellular immunity, or because adefovir inhibits HBV replication and significantly reduces HBV levels, and cellular immunity is reactivated, and further research is needed. For patients who use nucleoside (acid) analogues for the first time, it is recommended to use drugs with high antiviral activity and low drug resistance. Entecavir tablets can rapidly reduce blood HBV DNA levels, reduce the virus by more than 5 times after 12 weeks of treatment, and reduce the hepatitis B virus DNA level to below 75% in 75% of patients after 48 weeks of treatment. Studies have shown that, under the same treatment conditions, entecavir tablets represented by Runzhong are the fastest antiviral drugs among the existing antiviral drugs. HBV variants induced by long-term adefovir treatment are different from lamivudine. Peters et al. [29] reported that one asymptomatic carrier of HBV infection was treated with lamivudine for 6 months after renal transplantation due to recurrence of hepatitis B, and his condition improved for a time. However, one year later, liver disease became worse due to the emergence of lamivudine resistance and gradually progressed to liver failure. Therefore, lamivudine had to be stopped and liver transplantation performed. After liver transplantation, hepatitis B immunoglobulin plus adefovir were used for treatment. Sixteen months after liver transplantation, HBV DNA was still negative. The HBV polymerase gene sequence did not detect YMDD variants that are common in lamivudine resistance, but two other variants (F514 L and L528) M).

Adefovir in recent clinical trials found adverse reactions to kidney damage that deserve attention. Current clinical trial doses are 30 mg (11 patients) and 10 mg (12 patients) once daily. Participants in the experiment were 23 patients who could still detect HBV DNA after taking lamivudine. Eight of them had their doses lowered due to the effects of renal function after administration: six had their doses reduced from 30 mg to 10 mg.

Adefovir Research Progress

Review of Clinical Medical Progress in 2005: Hepatology

ntPCR-RFLP detection of adefovir resistance mutation in HBV-rtA181V mutation

Efficacy and safety of adefovir dipivoxil (detin) in the treatment of HBeAg-positive chronic hepatitis B in China ...

New progress in adefovir dipivoxil (heweili) global clinical research

Recent advances in adefovir dipivoxil clinical research

Progress of adefovir dipivoxil for chronic hepatitis B

Clinical research on adefovir in the treatment of chronic hepatitis B

Long course of ADV 10 mg for HBeAg positive chronic hepatitis B

American Conference on Liver Diseases: Recent Advances in Adefovir Disoproxil Clinical Research

Characteristics and Significance of Phase III Clinical Study of Adefovir Dipivoxil in China

Adefovir drug description

Adefovir indication

It is suitable for the treatment of adult chronic hepatitis B patients with replication evidence of hepatitis B virus activity, accompanied by persistent elevation of serum amino acid transferase (ATL or AST), or liver function compensation of liver histologically active lesions.

Adefovir dosage

Patients must use this product under the guidance of a doctor who has experience in treating chronic hepatitis B.

The recommended dosage for adults (18 to 65 years) is 10 mg once daily, orally before or after meals.

The optimal course of treatment has not yet been determined. Do not use more than the recommended dose.

Patients should be regularly monitored for hepatitis B biochemical indicators, virological indicators and serum markers, at least once every 6 months.

Adefovir side effects

I. Side effects of human immunodeficiency virus:

When taking adefovir dipivoxil anti-HBV treatment drugs, it will have an effect on the human immunodeficiency virus carried by patients with chronic hepatitis B, and there may be side effects of human immunodeficiency virus resistance.

Side effects of renal dysfunction:

Patients with renal dysfunction or a potential risk of renal dysfunction may have nephrotoxic side effects when taking adefovir dipivoxil for chronic treatment

Third, the side effects of lactic acidosis:

Adefovir dipivoxil is a nucleoside analog drug, and nucleoside analogs alone, or combined with other antiretroviral drugs, can cause patients with lactic acidosis and severe hepatomegaly with steatosis Side effects can seriously cause patient death.

Adefovir medication for pregnant and lactating women

There are insufficient data on the use of adefovir dipivoxil in pregnant women. Pregnant women do not use adefovir dipivoxil as much as possible. If it is needed, the pros and cons should be weighed. The use of adefovir dipivoxil during pregnancy can only be considered when the potential benefit is definitely greater than the risk to the fetus. Because the potential risk to developing human embryos is unclear, it is recommended that women of childbearing age treated with adefovir dipivoxil use effective contraception. It is not known whether adefovir is secreted into human milk during lactation. Therefore, mothers who are taking adefovir dipivoxil should be cautioned against breastfeeding.

Adefovir drug comparison

1. After taking adefovir, there is less variation in hepatitis B virus, which is better than lamivudine. Taking adefovir for 1 year, no mutation was seen, and 2.7% of patients took mutation for 2 years. Therefore, adefovir can be taken for a long time.

2. Hepatitis B virus mutation after taking lamivudine may cause treatment failure. Changing to adefovir may still be effective, which relieves the worries of taking lamivudine to a certain extent.

3. Adefovir has a small adverse effect. With placebo control, the side effects of the two are not significantly different.

At present, adefovir is not a substitute for lamivudine. Some people think that this is similar to the situation when penicillin was marketed. At first, penicillin was very effective against diseases caused by Gram-positive cocci. Later, the virus became resistant. , Penicillin efficacy decreased. Later, in order to deal with drug-resistant bacteria, scientists developed new penicillins and cephalosporins. Until now, even though the third-generation cephalosporins have been widely used, they cannot replace the old penicillins.

Adefovir resistance

When patients with hepatitis B take traditional nucleoside drugs such as adefovir dipivoxil, it is indeed more prone to certain resistance phenomena, especially for patients who take this drug for antiviral treatment for a long time. Or in the course of medication can not strictly follow the doctor's instructions, then the occurrence of drug resistance will be accelerated. When this happens, patients ca nt stop or change medicines blindly. Instead, they should go to a regular liver hospital to consult a professional doctor in time to undergo a comprehensive examination. After the doctor understands your specific medication situation, it will be based on your current Status for you to develop a scientific and reasonable withdrawal plan. If the patient discontinues the drug without authorization, it is likely to cause the patient's condition to rebound and even worsen the patient's condition.

In fact, taking traditional hepatitis B antiviral drugs, in addition to drug resistance, it also tends to bring some adverse reactions to patients, such as dizziness, headache, fatigue, respiratory symptoms, abdominal discomfort, nausea, and vomiting. In the process of taking this medicine, not only must pay attention to the problem of drug resistance, but also be affected by these adverse side effects, so you must be especially careful when using this medicine.

Adefovir related products

Adefovir dipivoxil

There are Heweili, Daiding, Agandin, more adefovir dipivoxil products such as Adicent, Jiule, Youheding, Dinghe, Yilaifen and so on.

Currently, a multi-center phase III clinical trial of adefovir is ongoing, and another double-blind randomized study involving 130 patients with ineffective lamivudine treatment is also underway. Participants will take 10 mg of Adefovir Dipivoxil and 100 mg of lamivudine daily. Adefovir Dipivoxil may bring new hope to lamivudine-resistant patients with chronic hepatitis B.

Adefovir ester price

The price of adefovir dipivoxil is various, and the price of adefovir dipivoxil is different in different regions. The price of 10mg * 14 tablets / box is about 165 yuan, and the price of 10mg * 7 tablets / box is about 88 yuan. Of course, some places sell more than 300, some places sell more than 400, the specific price can go to some large pharmacies or regular hospital consultation.

Adefovir dipivoxil is generally sold at a retail price of 100-200 and varies from region to region. Therefore, the price of adefovir dipivoxil should consider the actual situation of the patient's location. If you want to buy adefovir dipivoxil tablets, you must buy them at regular pharmacies and hospitals. At present, adefovir dipivoxil 10mg * 7 tablets / box is about 100 yuan, and 10mg * 14 tablets / The price of the box is around 200 yuan.

In China, the price of adefovir is a bit too expensive. Generally, the price of a box of adefovir is 130 ~ 200 yuan. Because the Lamivudine manufacturers in different hospitals and the economic level of different places are different, the specific purchase price fluctuates above this standard, and patients can refer to the following prices.

1. Agendine (Adefovir dipivoxil tablets) Fujian Guangshengtang Pharmaceutical Co., Ltd. 10mg * 14 tablets / box 135 yuan

2. Agandine (Adefovir dipivoxil) Fujian Guangshengtang Pharmaceutical Co., Ltd. 10mg * 10 / box of 167 yuan

3. Yougading (Adefovir dipivoxil) Shanghai Yishengyuan Pharmaceutical Co., Ltd. 10mg * 14 tablets / box of 160 yuan

4. Ding He (Adefovir dipivoxil) Shandong Lukang Chenxin Pharmaceutical Co., Ltd. 10mg * 7 tablets / box of 85 yuan ·

5. Daiding (adefovir dipivoxil) Tianjin Pharmaceutical Research Institute Pharmaceutical Co., Ltd. 10mg * 14 tablets / box 120 yuan

6. Daiding (Adefovir dipivoxil) Tianjin Pharmaceutical Research Institute Pharmaceutical Co., Ltd. 10mg * 7 tablets / box 100 yuan