Indications
Entecavir is prescribed for the treatment of chronic hepatitis B virus (HBV) infection in adults who show signs of active viral replication. This treatment is particularly indicated for patients who exhibit persistent elevations in serum aminotransferases (ALT or AST) or those with a histologically active disease.
Pharmacodynamics
As a guanosine nucleoside analogue, entecavir offers selective antiviral activity against HBV. It functions by inhibiting the replication process of the hepatitis B virus at all three critical steps, providing an effective mechanism of action. Notably, entecavir demonstrates a higher efficacy compared to lamivudine, an earlier HBV therapeutic agent.
Absorption
Upon oral administration, entecavir is rapidly absorbed, with peak plasma concentrations typically occurring between 0.5 to 1.5 hours in healthy individuals. The bioavailability of entecavir, when administered as a tablet, reaches 100% relative to its oral solution form, ensuring efficient delivery of the drug into systemic circulation.
Metabolism
Entecavir does not interact with the cytochrome P450 (CYP450) enzyme system, as it is neither a substrate, inhibitor, nor inducer. The drug undergoes efficient phosphorylation, converting to its active triphosphate form, which is essential for its antiviral efficacy.
Mechanism of Action
Entecavir functions by competitively inhibiting the natural substrate deoxyguanosine triphosphate, thereby effectively targeting all three essential activities of the HBV polymerase (reverse transcriptase): base priming, reverse transcription of the negative strand from the pregenomic messenger RNA, and synthesis of the positive strand of HBV DNA. Upon activation by cellular kinases, entecavir is incorporated into the viral DNA, leading to a marked suppression of HBV polymerase activity.
