Anastasia Rivkin1. 1. Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, NY 11201, USA. anastasia.rivkin@liu.edu
Abstract
BACKGROUND: Infection with the hepatitis B virus (HBV) affects two billion people worldwide, and an estimated 400 million people are chronically infected. Currently, FDA-approved regimens for the treatment of chronic HBV include interferon-alpha2b, peginterferon-alpha2a, lamivudine, adefovir dipivoxil, and recently, entecavir. OBJECTIVE: The purpose of this review is to evaluate the pharmacokinetic and pharmacodynamic properties, and the clinical efficacy and safety of entecavir in the treatment of nucleoside-naĩve and nucleoside-resistant HBeAg-positive and HBeAg-negative chronic hepatitis B (CHB). SEARCH METHODOLOGY: Computerized searches of PubMed and International Pharmaceutical Abstracts from 1985 to July 10, 2005, were performed with the search headings: entecavir, BMS-200475, and chronic hepatitis B. FINDINGS: Entecavir, a new deoxyguanosine analog, represents a third agent within the nucleoside/nucleotide HBV polymerase inhibitor class with distinct advantages over lamivudine and adefovir dipivoxil: it has a three-step mechanism of action, is the most potent inhibitor of HBV DNA polymerase, is not associated with any major adverse effects, and has a limited potential for resistance. In phase II and III clinical trials, entecavir was found to be superior to lamivudine for all primary endpoints evaluated in both nucleoside-naïve and lamivudine-resistant patients. Entecavir was effective in both HBeAg-positive and HBeAg-negative nucleoside-naïve patients. At this time, optimal duration of entecavir therapy is unknown. CONCLUSION: Entecavir represents a new first- or second-line treatment option for patients chronically infected with HBV. Long-term efficacy and safety studies as well as studies of entecavir in combination with interferon products or other nucleoside/nucleotide analogs are eagerly awaited.
BACKGROUND: Infection with the hepatitis B virus (HBV) affects two billion people worldwide, and an estimated 400 million people are chronically infected. Currently, FDA-approved regimens for the treatment of chronic HBV include interferon-alpha2b, peginterferon-alpha2a, lamivudine, adefovirdipivoxil, and recently, entecavir. OBJECTIVE: The purpose of this review is to evaluate the pharmacokinetic and pharmacodynamic properties, and the clinical efficacy and safety of entecavir in the treatment of nucleoside-naĩve and nucleoside-resistant HBeAg-positive and HBeAg-negative chronic hepatitis B (CHB). SEARCH METHODOLOGY: Computerized searches of PubMed and International Pharmaceutical Abstracts from 1985 to July 10, 2005, were performed with the search headings: entecavir, BMS-200475, and chronic hepatitis B. FINDINGS:Entecavir, a new deoxyguanosine analog, represents a third agent within the nucleoside/nucleotide HBV polymerase inhibitor class with distinct advantages over lamivudine and adefovirdipivoxil: it has a three-step mechanism of action, is the most potent inhibitor of HBV DNA polymerase, is not associated with any major adverse effects, and has a limited potential for resistance. In phase II and III clinical trials, entecavir was found to be superior to lamivudine for all primary endpoints evaluated in both nucleoside-naïve and lamivudine-resistant patients. Entecavir was effective in both HBeAg-positive and HBeAg-negative nucleoside-naïve patients. At this time, optimal duration of entecavir therapy is unknown. CONCLUSION:Entecavir represents a new first- or second-line treatment option for patients chronically infected with HBV. Long-term efficacy and safety studies as well as studies of entecavir in combination with interferon products or other nucleoside/nucleotide analogs are eagerly awaited.