Please use this identifier to cite or link to this item:
|Title:||Pharmacokinetics of telbivudine following oral administration of escalating single and multiple doses in patients with chronic hepatitis B virus infection: Pharmacodynamic implications||Authors:||Zhou, X.-J.
|Issue Date:||Mar-2006||Citation:||Zhou, X.-J., Lim, S.-G., Lloyd, D.M., Chao, G.C., Brown, N.A., Lai, C.-L. (2006-03). Pharmacokinetics of telbivudine following oral administration of escalating single and multiple doses in patients with chronic hepatitis B virus infection: Pharmacodynamic implications. Antimicrobial Agents and Chemotherapy 50 (3) : 874-879. ScholarBank@NUS Repository. https://doi.org/10.1128/AAC.50.3.874-879.2006||Abstract:||The pharmacokinetics of telbivudine were evaluated in adult patients with chronic hepatitis B virus (HBV) infection following once-daily oral administration at escalating doses of 25, 50, 100, 200, 400, and 800 mg/day for 4 weeks. Telbivudine was rapidly absorbed after oral administration, with the median times Tmax to the maximum plasma concentration (C max) ranging from 0.8 to 3.0 h postdosing across cohorts. Single-dose and steady-state maximum Cmaxs and the areas under the plasma concentration-time curve from time zero to time t (AUC0-ts) increased proportionally with dose. At steady-state, the values of Cmax and AUC0-t were higher than those obtained after the administration of a single dose, indicative of a slight accumulation, with the ratios of the steady-state value to the value after the administration of a single dose ranging from 1.14 to 1.49 for Cmax and from 1.40 to 1.70 for AUC 0-t. While the elimination of telbivudine from plasma was apparently monophasic over the 8-h sampling period, the substantial steady-state trough plasma levels observed in the groups receiving doses of 100 to 800 mg were clearly indicative of the presence of a second slower elimination phase, with the mean estimated half-lives ranging from 29.5 to 41.3 h by compartmental modeling analysis. Pharmacokinetic and pharmacodynamic analyses by using maximum-effect modeling established a quantitative relationship between a reduction in serum HBV DNA levels and parameters of drug exposure, in particular, the steady-state Cmax and AUC0-t. In summary, this study showed that telbivudine exhibits dose-proportional plasma pharmacokinetics with sustained steady-state drug exposure and exposure-related antiviral activity, supporting the need for further clinical studies by use of a once-daily regimen in patients with chronic HBV infection. Copyright © 2006, American Society for Microbiology. All Rights Reserved.||Source Title:||Antimicrobial Agents and Chemotherapy||URI:||http://scholarbank.nus.edu.sg/handle/10635/132533||ISSN:||00664804||DOI:||10.1128/AAC.50.3.874-879.2006|
|Appears in Collections:||Staff Publications|
Show full item record
Files in This Item:
There are no files associated with this item.
checked on Jun 3, 2020
WEB OF SCIENCETM
checked on Jun 3, 2020
checked on Jun 5, 2020
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.