The emergence of viral resistance with various treatment options has led to clinical limitations and failed therapy. This has been a problem, particularly if one is targeting a sustained viral response against HBV infection. So far with ente-cavir, cross-resistance with HBV nucleo-side analogues has been observed. Resistance emerges in 14% to 32% of HBV-infected patients who have received lamivudine for one year, and this figure increases to approximately 70% at five years.

Adefovir dipivoxil-resistant strains emerge at a lower rate (from 4% at three years). In cell-based assays, however, entecavir revealed eight-fold to 30-fold less inhibition of replication to HBV containing lamivudine resistance mutations rtL180M and/or rtM204V/I than of wild-type virus. Entecavir also remains susceptible to adefovir-resistant genomes to HBV encoding the rtN236T or rtA181V strain. canadian pharmacy viagra

In vitro testing has shown that patients who had been considered lamivudine-refractory and who had not responded to entecavir were responsive to adefovir dipivoxil but still retained resistance to lamivudine. In clinical trials of nucleo-side-naive patients, entecavir demonstrated no evidence of phenotypic and genotypic changes detected with ente-cavir-resistant strains. However, lamivu-dine-refractory patients showed possible evidence of emerging resistance to ente-cavir by week 48, especially in the presence of lamivudine mutations identified as rtL180M and/or rtM204V/I.

PHARMACOKINETICS

In healthy subjects, peak plasma concentrations of entecavir occur between 0.5 and 1.5 hours after oral administration, and steady-state concentrations are observed after six to 10 days. Entecavir has an accumulation half-life of approximately 24 hours, thus allowing for once-daily dosing.

In addition, the bioavailability of oral entecavir tablets is equal to that of the oral solution; thus, the two dosage forms are considered interchangeable.

Entecavir does not appear to be a substrate, inhibitor, or inducer of the cyto-chrome P450 (CYP450) system, and it is not metabolized through either oxida-tive or acetylation mechanisms. Minor glucoronidative and sulfate conjugates of entecavir have been observed in clinical trials. 

Entecavir is primarily eliminated, unchanged, by the kidneys; it is cleared by filtration and renal tubular secretion in a non-dose-dependent fashion. Thus, the agent’s half-life is prolonged in renally impaired patients, and the dose should be adjusted according to the degree of impairment.