Adefovir is a prescription medicine used to treat (chronic) infections with hepatitis B virus. A prodrug form of adefovir was previously called bis-POM PMEA, with trade names Preveon and Hepsera. It is an orally administered nucleotide analog reverse-transcriptase inhibitor (ntRTI). It can be formulated as the pivoxil prodrug adefovir dipivoxil.

Uses

It is used for treatment of

hepatitis B Hepatitis B is an infectious disease caused by the '' Hepatitis B virus'' (HBV) that affects the liver; it is a type of viral hepatitis. It can cause both acute and chronic infection. Many people have no symptoms during an initial infection. F ...

. Trials of adefovir in patients with

HIV The human immunodeficiency viruses (HIV) are two species of '' Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immu ...

have not shown any clear benefits.

History

Adefovir was invented in the Institute of Organic Chemistry and Biochemistry,

Academy of Sciences of the Czech Republic The Czech Academy of Sciences (abbr. CAS, cs, Akademie věd České republiky, abbr. AV ČR) was established in 1992 by the Czech National Council as the Czech successor of the former Czechoslovak Academy of Sciences and its tradition goes bac ...

by Antonín Holý, and the drug was developed by

Gilead Sciences Gilead Sciences, Inc. () is an American biopharmaceutical company headquartered in Foster City, California, that focuses on researching and developing antiviral drugs used in the treatment of HIV/AIDS, hepatitis B, hepatitis C, influenza, and ...

for HIV with the brand name Preveon. However, in November 1999, an expert panel advised the U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

(FDA) not to approve the drug due to concerns about the severity and frequency of kidney toxicity when dosed at 60 or 120 mg. The FDA followed that advice, refusing to approve adefovir as a treatment for HIV. Gilead Sciences discontinued its development for HIV treatment in December 1999, but continued to develop the drug for hepatitis B (HBV), where it is effective with a much lower dose of 10 mg. FDA approval for use in the treatment of hepatitis B was granted on September 20, 2002, and adefovir is sold for this indication under the brand name Hepsera. Adefovir became an approved treatment for HBV in the European Union in March 2003.

Mechanism of action

Adefovir works by blocking

reverse transcriptase A reverse transcriptase (RT) is an enzyme used to generate complementary DNA (cDNA) from an RNA template, a process termed reverse transcription. Reverse transcriptases are used by viruses such as HIV and hepatitis B to replicate their genomes, ...

, an enzyme crucial for the HBV to reproduce in the body. It is approved for the treatment of chronic hepatitis B in adults with evidence of active viral replication and either evidence of persistent elevations in serum

aminotransferase Transaminases or aminotransferases are enzymes that catalyze a transamination reaction between an amino acid and an α- keto acid. They are important in the synthesis of amino acids, which form proteins. Function and mechanism An amino acid ...

s (primarily ALT) or histologically active disease. The main benefit of adefovir over

lamivudine Lamivudine, commonly called 3TC, is an antiretroviral medication used to prevent and treat HIV/AIDS. It is also used to treat chronic hepatitis B when other options are not possible. It is effective against both HIV-1 and HIV-2. It is typical ...

(the first NRTI approved for the treatment of HBV) is that it takes a much longer period of time for the virus to develop resistance to it. Adefovir dipivoxil contains two pivaloyloxymethyl units, making it a prodrug form of adefovir.

References

External links

* - Adefovir dipivoxil {{Antivirals Gilead Sciences Reverse transcriptase inhibitors Purines Phosphonic acids