New drugs for chronic hepatitis B: a review.
Three nucleotide/nucleoside analogs are used for chronic hepatitis B (HBV): lamivudine, adefovir dipivoxil, and entecavir. Lamivudine and adefovir are advantageous for oral administration and safety but induce a sustained response after withdrawal of therapy in only a minority of patients. Thus, the treatment should be given in trials in a majority of patients for a long period of time. In addition, the long-term efficacy of lamivudine is limited by the frequent emergence of drug-resistant HBV mutants. Adefovir is associated with a low frequency of resistance, but its antiviral effect is not optimal. Entecavir, a cyclopentyl guanosine analog, is a potent inhibitor of HBV-DNA polymerase and it inhibits both priming and elongation steps of viral DNA replication. In phase II and III clinical trials, entecavir was found to be superior to lamivudine for all primary end points evaluated in both nucleoside-naive and lamivudine-resistant patients, and it was effective in both HBeAg-positive and HBeAg-negative nucleoside-naive patients. Only one trial has shown cases of viral resistance to this drug. The approved dosage in treatment-naive patients is 0.5 mg per day orally, whereas in patients who have failed lamivudine therapy or who are known to harbor lamivudine-resistant mutants, the approved dosage is 1.0 mg per day. Recent preliminary results show that clevudine, telbivudine, and emtricitabine may be potent analogs available for the treatment of HBV. Further studies are being conducted to assess the long-term efficacy and safety of these drugs.
Palumbo
Emilio
E
Clinic of Paediatric, Hospital of Sondrio, Foggia, Italy. emipalu2003@yahoo.it
D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D000998:Antiviral Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001086:Arabinofuranosyluracil / Q000009:adverse effects / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D000068679:Emtricitabine; D006147:Guanine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D019259:Lamivudine / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D009705:Nucleosides / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D063065:Organophosphonates / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D011744:Pyrimidinones / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D000077712:Telbivudine; D013936:Thymidine / Q000031:analogs & derivatives
D000998:Antiviral Agents; D009705:Nucleosides; D063065:Organophosphonates; D011744:Pyrimidinones; D003841:Deoxycytidine; D000077712:Telbivudine; D019259:Lamivudine; D001086:Arabinofuranosyluracil; C413685:entecavir; D006147:Guanine; D000068679:Emtricitabine; C034935:clevudine; D000225:Adenine; C106812:adefovir dipivoxil; D013936:Thymidine