Description

Adefovir dipivoxil (trade name Hepsera) is an oral prodrug of the nucleotide analogue adefovir. It is an antiviral medication used to treat chronic hepatitis B virus (HBV) infection. As a prodrug, it is an inactive compound that is converted into its active form, adefovir, after being absorbed by the body. Adefovir belongs to a class of drugs called nucleoside reverse transcriptase inhibitors (NRTIs).

Indication

Adefovir dipivoxil is indicated for the treatment of chronic hepatitis B in adults and children at least 12 years of age who show signs of active viral replication and have either elevated liver enzymes (serum aminotransferases) or histologically active disease. It is used in both patients with e-antigen-positive and e-antigen-negative chronic hepatitis B. It has also shown efficacy in patients with lamivudine-resistant HBV infection.

Mechanism of Action

Adefovir dipivoxil’s mechanism of action involves a multi-step process:

1. Conversion to Adefovir: After oral administration, adefovir dipivoxil is rapidly absorbed and hydrolyzed (broken down) in the body to its active antiviral agent, adefovir. This conversion happens primarily in the intestines and liver.

2. Phosphorylation: Once converted to adefovir, it is then phosphorylated by cellular enzymes (kinases) to its active diphosphate form, adefovir diphosphate (adefovir-DP).

3. Inhibition of Viral DNA Polymerase: Adefovir diphosphate is the key to the drug’s antiviral effect. It acts as a competitive inhibitor of the HBV DNA polymerase (also known as reverse transcriptase), a viral enzyme crucial for the replication of the hepatitis B virus. Adefovir diphosphate mimics the natural substrate of this enzyme, deoxyadenosine triphosphate (dATP).

4. Chain Termination: By competing with dATP, adefovir diphosphate is incorporated into the growing viral DNA chain. However, its incorporation causes premature DNA chain termination. This halts the elongation of the viral DNA strand, preventing the virus from replicating and reducing the viral load in the body.