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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

TitlePharmacokinetics of telbivudine following oral administration of escalating single and multiple doses in patients with chronic hepatitis B virus infection: Pharmacodynamic implications
Authors
Issue Date2006
PublisherAmerican Society for Microbiology.
Citation
Antimicrobial Agents And Chemotherapy, 2006, v. 50 n. 3, p. 874-879 How to Cite?
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.
Persistent Identifierhttp://hdl.handle.net/10722/49050
ISSN
2014 Impact Factor: 4.476
2014 SCImago Journal Rankings: 2.005
PubMed Central ID
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorZhou, XJen_HK
dc.contributor.authorLim, SGen_HK
dc.contributor.authorLloyd, DMen_HK
dc.contributor.authorChao, GCen_HK
dc.contributor.authorBrown, NAen_HK
dc.contributor.authorLai, CLen_HK
dc.date.accessioned2008-06-12T06:33:20Z-
dc.date.available2008-06-12T06:33:20Z-
dc.date.issued2006en_HK
dc.identifier.citationAntimicrobial Agents And Chemotherapy, 2006, v. 50 n. 3, p. 874-879en_HK
dc.identifier.issn0066-4804en_HK
dc.identifier.urihttp://hdl.handle.net/10722/49050-
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.en_HK
dc.format.extent388 bytes-
dc.format.mimetypetext/html-
dc.languageengen_HK
dc.publisherAmerican Society for Microbiology.en_HK
dc.relation.ispartofAntimicrobial Agents and Chemotherapyen_HK
dc.rightsAntimicrobial Agents and Chemotherapy. Copyright © American Society for Microbiology.en_HK
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. 874-879en_HK
dc.subject.meshAntiviral Agents - administration & dosage - adverse effects - pharmacokinetics - pharmacology - therapeutic useen_HK
dc.subject.meshNucleosides - administration & dosage - adverse effects - pharmacokinetics - pharmacology - therapeutic useen_HK
dc.subject.meshPyrimidinones - administration & dosage - adverse effects - pharmacokinetics - pharmacology - therapeutic useen_HK
dc.subject.meshAdministration, Oralen_HK
dc.subject.meshArea Under Curveen_HK
dc.titlePharmacokinetics of telbivudine following oral administration of escalating single and multiple doses in patients with chronic hepatitis B virus infection: Pharmacodynamic implicationsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0066-4804&volume=50&issue=3&spage=874&epage=879&date=2006&atitle=Pharmacokinetics+of+telbivudine+following+oral+administration+of+escalating+single+and+multiple+doses+in+patients+with+chronic+hepatitis+B+virus+infection:+pharmacodynamic+implicationsen_HK
dc.identifier.emailLai, CL:hrmelcl@hku.hken_HK
dc.identifier.authorityLai, CL=rp00314en_HK
dc.description.naturepublished_or_final_versionen_HK
dc.identifier.doi10.1128/AAC.50.3.874-879.2006en_HK
dc.identifier.pmid16495245en_HK
dc.identifier.pmcidPMC1426427en_HK
dc.identifier.scopuseid_2-s2.0-33644662858en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33644662858&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume50en_HK
dc.identifier.issue3en_HK
dc.identifier.spage874en_HK
dc.identifier.epage879en_HK
dc.identifier.isiWOS:000235786300007-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridZhou, XJ=35291162500en_HK
dc.identifier.scopusauthoridLim, SG=7404081127en_HK
dc.identifier.scopusauthoridLloyd, DM=7402321593en_HK
dc.identifier.scopusauthoridChao, GC=36643443300en_HK
dc.identifier.scopusauthoridBrown, NA=7403548663en_HK
dc.identifier.scopusauthoridLai, CL=7403086396en_HK

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