Pharmacokinetics of telbivudine in subjects with various degrees of hepatic impairment

Antimicrob Agents Chemother. 2006 May;50(5):1721-6. doi: 10.1128/AAC.50.5.1721-1726.2006.

Abstract

This study evaluated the effect of hepatic impairment on the pharmacokinetics of telbivudine, an investigational nucleoside antiviral for the treatment of chronic hepatitis B virus infection. Twenty-four subjects were assigned to four hepatic function groups (normal function and mild, moderate, and severe impairment, with six subjects in each group) on the basis of Child-Pugh scores. The subjects were administered a single oral dose of 600 mg telbivudine, and blood samples were collected over a 48-h interval for pharmacokinetic analyses. Telbivudine was well tolerated by all subjects. Telbivudine plasma concentration-time profiles were similar across the four hepatic function groups. The principal pharmacokinetic parameters of drug exposure, i.e., the maximum plasma concentration and area under the drug concentration-time curve, were comparable between subjects with various degrees of hepatic impairment and those with normal hepatic function. Results from this single-dose pharmacokinetic assessment therefore provide a pharmacologic rationale for further evaluation of the safety and efficacy of telbivudine in hepatitis B virus-infected patients with decompensated liver diseases.

Publication types

  • Clinical Trial, Phase I
  • Comparative Study

MeSH terms

  • Administration, Oral
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / adverse effects
  • Antiviral Agents / blood
  • Antiviral Agents / pharmacokinetics*
  • Area Under Curve
  • Case-Control Studies
  • Chromatography, High Pressure Liquid
  • Female
  • Humans
  • Liver Diseases / metabolism*
  • Male
  • Mass Spectrometry
  • Middle Aged
  • Nucleosides / administration & dosage
  • Nucleosides / adverse effects
  • Nucleosides / blood
  • Nucleosides / pharmacokinetics*
  • Pyrimidinones / administration & dosage
  • Pyrimidinones / adverse effects
  • Pyrimidinones / blood
  • Pyrimidinones / pharmacokinetics*
  • Severity of Illness Index
  • Telbivudine
  • Thymidine / analogs & derivatives

Substances

  • Antiviral Agents
  • Nucleosides
  • Pyrimidinones
  • Telbivudine
  • Thymidine