Please use this identifier to cite or link to this item: https://doi.org/10.1128/AAC.50.3.874-879.2006
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.
Lim, S.-G. 
Lloyd, D.M.
Chao, G.C.
Brown, N.A.
Lai, C.-L.
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
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