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Article: Pharmacokinetics of telbivudine following oral administration of escalating single and multiple doses in patients with chronic hepatitis B virus infection: Pharmacodynamic implications
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TitlePharmacokinetics of telbivudine following oral administration of escalating single and multiple doses in patients with chronic hepatitis B virus infection: Pharmacodynamic implications
 
AuthorsZhou, XJ3
Lim, SG2
Lloyd, DM3
Chao, GC3
Brown, NA3
Lai, CL1
 
Issue Date2006
 
PublisherAmerican Society for Microbiology.
 
CitationAntimicrobial Agents And Chemotherapy, 2006, v. 50 n. 3, p. 874-879 [How to Cite?]
DOI: http://dx.doi.org/10.1128/AAC.50.3.874-879.2006
 
AbstractThe 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 T max to the maximum plasma concentration (C max) ranging from 0.8 to 3.0 h postdosing across cohorts. Single-dose and steady-state maximum C maxs and the areas under the plasma concentration-time curve from time zero to time t (AUC 0-ts) increased proportionally with dose. At steady-state, the values of C max and AUC 0-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 C max 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 C max and AUC 0-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.
 
ISSN0066-4804
2012 Impact Factor: 4.565
2012 SCImago Journal Rankings: 1.963
 
DOIhttp://dx.doi.org/10.1128/AAC.50.3.874-879.2006
 
PubMed Central IDPMC1426427
 
ISI Accession Number IDWOS:000235786300007
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorZhou, XJ
 
dc.contributor.authorLim, SG
 
dc.contributor.authorLloyd, DM
 
dc.contributor.authorChao, GC
 
dc.contributor.authorBrown, NA
 
dc.contributor.authorLai, CL
 
dc.date.accessioned2008-06-12T06:33:20Z
 
dc.date.available2008-06-12T06:33:20Z
 
dc.date.issued2006
 
dc.description.abstractThe 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 T max to the maximum plasma concentration (C max) ranging from 0.8 to 3.0 h postdosing across cohorts. Single-dose and steady-state maximum C maxs and the areas under the plasma concentration-time curve from time zero to time t (AUC 0-ts) increased proportionally with dose. At steady-state, the values of C max and AUC 0-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 C max 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 C max and AUC 0-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.
 
dc.description.naturepublished_or_final_version
 
dc.format.extent388 bytes
 
dc.format.mimetypetext/html
 
dc.identifier.citationAntimicrobial Agents And Chemotherapy, 2006, v. 50 n. 3, p. 874-879 [How to Cite?]
DOI: http://dx.doi.org/10.1128/AAC.50.3.874-879.2006
 
dc.identifier.doihttp://dx.doi.org/10.1128/AAC.50.3.874-879.2006
 
dc.identifier.epage879
 
dc.identifier.isiWOS:000235786300007
 
dc.identifier.issn0066-4804
2012 Impact Factor: 4.565
2012 SCImago Journal Rankings: 1.963
 
dc.identifier.issue3
 
dc.identifier.openurl
 
dc.identifier.pmcidPMC1426427
 
dc.identifier.pmid16495245
 
dc.identifier.scopuseid_2-s2.0-33644662858
 
dc.identifier.spage874
 
dc.identifier.urihttp://hdl.handle.net/10722/49050
 
dc.identifier.volume50
 
dc.languageeng
 
dc.publisherAmerican Society for Microbiology.
 
dc.publisher.placeUnited States
 
dc.relation.ispartofAntimicrobial Agents and Chemotherapy
 
dc.relation.referencesReferences in Scopus
 
dc.rightsAntimicrobial Agents and Chemotherapy. Copyright © American Society for Microbiology.
 
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License
 
dc.rightsCopyright © American Society for Microbiology, Antimicrobial Agents and Chemotherapy, 2006, v. 50 n. 3, p. 874-879
 
dc.subject.meshAntiviral Agents - administration & dosage - adverse effects - pharmacokinetics - pharmacology - therapeutic use
 
dc.subject.meshNucleosides - administration & dosage - adverse effects - pharmacokinetics - pharmacology - therapeutic use
 
dc.subject.meshPyrimidinones - administration & dosage - adverse effects - pharmacokinetics - pharmacology - therapeutic use
 
dc.subject.meshAdministration, Oral
 
dc.subject.meshArea Under Curve
 
dc.titlePharmacokinetics of telbivudine following oral administration of escalating single and multiple doses in patients with chronic hepatitis B virus infection: Pharmacodynamic implications
 
dc.typeArticle
 
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Author Affiliations
  1. The University of Hong Kong
  2. National University Hospital, Singapore
  3. Idenix Pharmaceuticals, Inc.