Adefovir
Encyclopedia
Adefovir dipivoxil, previously called bis-POM PMEA, with trade names Preveon and Hepsera, is an orally-administered nucleotide analog reverse transcriptase inhibitor
(ntRTI).
infection.
It is a failed treatment for HIV
.
by Antonín Holý
, and the drug was developed by Gilead Sciences
for HIV
with the brand name Preveon. However, in November 1999, an expert panel advised the U.S. Food and Drug Administration
(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 United States in September 2002 and in the European Union in March 2003.
Adefovir works by blocking reverse transcriptase
, an enzyme that is crucial for the hepatitis B virus (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 aminotransferases (primarily ALT) or histologically active disease.
The main benefit of adefovir over lamivudine
(the first NRTI approved for the treatment of hepatitis B) is that it takes a much longer period of time before the virus develops resistance to it.
Adefovir dipivoxil contains two pivaloyloxymethyl
units, making it a prodrug
form of Adefovir.
Reverse transcriptase inhibitor
Reverse-transcriptase inhibitors are a class of antiretroviral drug used to treat HIV infection, tumors, and cancer. RTIs inhibit activity of reverse transcriptase, a viral DNA polymerase enzyme that retroviruses need to reproduce.-Mechanism:...
(ntRTI).
Uses
It is used for treatment of hepatitis B and herpes simplex virusHerpes simplex virus
Herpes simplex virus 1 and 2 , also known as Human herpes virus 1 and 2 , are two members of the herpes virus family, Herpesviridae, that infect humans. Both HSV-1 and HSV-2 are ubiquitous and contagious...
infection.
It is a failed treatment for HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
.
History
Adefovir was invented in the Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech RepublicAcademy of Sciences of the Czech Republic
The Academy of Sciences of the Czech Republic was established in 1992 by the Czech National Council as the Czech successor of the former Czechoslovak Academy of Sciences. The Academy is the leading non-university public research institution in the Czech Republic...
by Antonín Holý
Antonín Holý
Antonín Holý is a Czech scientist. He specialises in the field of chemistry and cooperated on the development of important antiretroviral drugs used in the treatment of HIV and hepatitis B. He was involved in the creation of the most effective drug in the treatment of AIDS...
, and the drug was developed by Gilead Sciences
Gilead Sciences
Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes therapeutics. For many years since the company was founded, the company concentrated primarily on antiviral drugs to treat patients infected with HIV, hepatitis B or influenza. In 2006, Gilead acquired two...
for HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
with the brand name Preveon. However, in November 1999, an expert panel advised the U.S. Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
(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
Gilead Sciences
Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes therapeutics. For many years since the company was founded, the company concentrated primarily on antiviral drugs to treat patients infected with HIV, hepatitis B or influenza. In 2006, Gilead acquired two...
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 United States in September 2002 and in the European Union in March 2003.
Mechanism of action
Reverse transcriptase
In the fields of molecular biology and biochemistry, a reverse transcriptase, also known as RNA-dependent DNA polymerase, is a DNA polymerase enzyme that transcribes single-stranded RNA into single-stranded DNA. It also helps in the formation of a double helix DNA once the RNA has been reverse...
, an enzyme that is crucial for the hepatitis B virus (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 aminotransferases (primarily ALT) or histologically active disease.
The main benefit of adefovir over lamivudine
Lamivudine
Lamivudine is a potent nucleoside analog reverse transcriptase inhibitor .It is marketed by GlaxoSmithKline with the brand names Zeffix, Heptovir, Epivir, and Epivir-HBV.Lamivudine has been used for treatment of chronic hepatitis B at a lower dose than for treatment of HIV...
(the first NRTI approved for the treatment of hepatitis B) is that it takes a much longer period of time before the virus develops resistance to it.
Adefovir dipivoxil contains two pivaloyloxymethyl
Pivaloyloxymethyl
Pivaloyloxymethyl is a protecting group used in organic synthesis. The POM radical has the formula 3C-CO-O-CH2.The POM group is also sometimes used to produce prodrugs...
units, making it a prodrug
Prodrug
A prodrug is a pharmacological substance administered in an inactive form. Once administered, the prodrug is metabolised in vivo into an active metabolite, a process termed bioactivation. The rationale behind the use of a prodrug is generally for absorption, distribution, metabolism, and...
form of Adefovir.