Entecavir

Entecavir is an oral antiviral drug used in the treatment of hepatitis B infection.

Entecavir is a guanine analogue that inhibits all three steps in the viral replication process, and the manufacturer claims that it is more efficacious than previous agents used to treat hepatitis B (lamivudine and adefovir).

Entecavir is a nucleoside analogue used in the treatment of chronic hepatitis B for patients with active viral replication, histological evidence of active disease, or persistent elevations in liver transaminases.

For the treatment of chronic hepatitis B virus infection in adults with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease.

• Hepatitis B Chronic Infection

Entecavir is a guanosine nucleoside analogue with selective activity against hepatitis B virus (HBV). It is designed to selectively inhibit the Hepatitis B virus, blocking all three steps in the replication process. Entecavir is more efficient than an older Hepatitis B drug, lamivudine.

By competing with the natural substrate deoxyguanosine triphosphate, entecavir functionally inhibits all three activities of the HBV polymerase (reverse transcriptase, rt): (1) base priming, (2) reverse transcription of the negative strand from the pregenomic messenger RNA, and (3) synthesis of the positive strand of HBV DNA. Upon activation by kinases, the drug can be incorporated into the DNA which has the ultimate effect of inhibiting the HBV polymerase activity.

Absorption Following oral administration in healthy subjects, entecavir peak plasma concentrations occurred between 0.5 and 1.5 hours. In healthy subjects, the bioavailability of the tablet is 100% relative to the oral solution.

Binding of entecavir to human serum proteins in vitro is approximately 13%.

After reaching peak concentration, entecavir plasma concentrations decreased in a bi-exponential manner with a terminal elimination half-life of approximately 128-149 hours. The phosphorylated metabolite has a half-life of 15 hours.

• renal cl=383.2 +/- 101.8 mL/min [Unimpaired renal function]
• renal cl=197.9 +/- 78.1 mL/min [Mild impaired renal function]
• renal cl=135.6 +/- 31.6 mL/min [Moderate impaired renal function]
• renal cl=40.3 +/- 10.1 mL/min [severe impaired renal function]
• apparent oral cl=588.1 +/- 153.7 mL/min [Unimpaired renal function]
• apparent oral cl=309.2 +/- 62.6 mL/min [Mild impaired renal function]
• apparent oral cl=226.3 +/- 60.1 mL/min [Moderate impaired renal function]
• apparent oral cl=100.6 +/- 29.1 mL/min [severe impaired renal function]
• apparent oral cl=50.6 +/- 16.5 mL/min [severe impaired renal function amnaged with Hemodialysis]
• apparent oral cl=35.7 +/- 19.6 mL/min [severe impaired renal function amnaged with CAPD]

Healthy subjects who received single entecavir doses up to 40 mg or multiple doses up to 20 mg/day for up to 14 days had no increase in or unexpected adverse events. If overdose occurs, the patient must be monitored for evidence of toxicity, and standard supportive treatment applied as necessary.

• Take on an empty stomach. Take 2 hours before or 2 hours after a meal.