Entecavir

Entecavir ( CAS No. 142217-69-4) is a potent and selective inhibitor of HBV DNA polymerase (reverse transcriptase), whose core bioactivity is to inhibit replication of chronic hepatitis B virus (HBV). Its targets include the priming of HBV reverse transcriptase, and the synthesis steps of negative- and positive-strand DNA. It is effective against both wild-type HBV and lamivudine-resistant HBV (M204V/L180M mutations). In HepG2.2.15 cells, the EC?? for inhibition of HBV replication is 3.75 nM, and the EC?? for lamivudine-resistant strains increases by about 8-fold; no definitive MIC data are available. In vitro cell experiments are designed around the EC?? in the 0.1~10 nM range, while in animal experiments, rat/dog models use doses of 1~10 mg/kg/day. In a woodchuck chronic HBV infection model, oral administration can significantly reduce viral load and cccDNA levels. Clinically effective therapeutic concentrations correspond to oral doses of 0.5 mg/day (taken on an empty stomach) in nucleos(t)ide-na?ve adults, and 1 mg/day in lamivudine-resistant patients or those with decompensated liver disease. The steady-state peak plasma concentration is about 8.24 ng/mL. After 2 years of treatment, 81% of patients can achieve HBV DNA levels below 300 copies/mL, and the 5-year resistance rate in nucleos(t)ide-na?ve patients is only 0.9%. Development of resistance requires multiple mutations in HBV polymerase (e.g., T184G/S202I/M250V). Entecavir has a good safety profile, with occasional thrombocytopenia and lactic acidosis (high-risk populations require monitoring). It is indicated for patients with chronic HBV infection (with viral replication, elevated ALT, or histologically active liver disease) and for those with decompensated cirrhosis.

References:

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