Description

Telbivudine (trade names Sebivo in Europe and Tyzeka in the United States) is an oral antiviral medication used for the treatment of chronic hepatitis B virus (HBV) infection. It is a synthetic nucleoside analogue of thymidine, which is a building block of DNA. Telbivudine is known for its potent and specific activity against HBV.

Indication

Telbivudine is indicated for the treatment of chronic hepatitis B in adult patients with compensated liver disease and evidence of viral replication. This includes patients who show persistently elevated serum alanine aminotransferase (ALT) levels or have histological evidence of active liver inflammation and/or fibrosis.

It is important to note that while telbivudine was a significant treatment option, it has a relatively lower genetic barrier to resistance compared to other newer HBV drugs like entecavir and tenofovir. For this reason, its use is often recommended when alternative agents with a higher genetic barrier are not available or appropriate.

Mechanism of Action

The mechanism of action of telbivudine is based on its ability to inhibit the replication of the hepatitis B virus. The process occurs in three main steps:

1. Phosphorylation: After oral administration, telbivudine is taken up by the host cells and is phosphorylated by cellular enzymes (kinases) into its active form, telbivudine triphosphate.

2. Competitive Inhibition: Telbivudine triphosphate acts as a competitive inhibitor of the HBV DNA polymerase (reverse transcriptase). It competes with the natural substrate of the enzyme, deoxythymidine triphosphate (dTTP), for binding to the active site.

3. DNA Chain Termination: Once incorporated into the growing viral DNA chain, telbivudine triphosphate acts as a DNA chain terminator. This is because it lacks a 3′-hydroxyl group, which is required for the formation of the next phosphodiester bond. This premature termination of the DNA chain effectively stops the synthesis of new viral DNA, thereby halting viral replication and reducing the viral load.

Telbivudine has been shown to inhibit both first- and second-strand DNA synthesis by the HBV polymerase, with a preference for inhibiting second-strand synthesis.