Entecavir pharmacokinetics, safety, and tolerability after multiple ascending doses in healthy subjects

J Clin Pharmacol. 2006 Nov;46(11):1250-8. doi: 10.1177/0091270006293304.


A double-blind, placebo-controlled, multiple oral dose escalation study was conducted to investigate the pharmacokinetics, safety, and tolerability of entecavir in healthy subjects. Eight subjects were assigned to each of the 3 dose panels (0.1 mg, 0.5 mg, and 1 mg or matched placebo once daily for 14 days). Blood and urine samples were collected for pharmacokinetic analyses. Entecavir was rapidly absorbed, with peak plasma concentration occurring within 1 hour of dosing. Steady-state plasma concentrations of entecavir were achieved by 10 days following the initial dose. At steady state, the mean area under the plasma concentration-time curve over 1 dosing interval, increased approximately proportional to dose. Entecavir had a mean terminal half-life ranging from 128 to 149 hours and an effective half-life of approximately 24 hours. Elimination was predominantly through renal excretion, with mean urinary recovery ranging from 62% to 73%. Entecavir was safe and well tolerated when administered at doses ranging from 0.1 mg to 1 mg/d for 14 days.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / adverse effects*
  • Antiviral Agents / blood
  • Antiviral Agents / pharmacokinetics*
  • Dose-Response Relationship, Drug
  • Guanine / administration & dosage
  • Guanine / adverse effects
  • Guanine / analogs & derivatives*
  • Guanine / blood
  • Guanine / pharmacokinetics
  • Humans
  • Male
  • Middle Aged


  • Antiviral Agents
  • entecavir
  • Guanine