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dc.contributor.authorSahin, Selma
dc.contributor.authorBenet, Leslie Z.
dc.date.accessioned2019-12-16T10:18:19Z
dc.date.available2019-12-16T10:18:19Z
dc.date.issued2008
dc.identifier.issn0724-8741
dc.identifier.urihttps://doi.org/10.1007/s11095-008-9787-9
dc.identifier.urihttp://hdl.handle.net/11655/20048
dc.description.abstractHalf-life (t (1/2)) is the oldest but least well understood pharmacokinetic parameter, because most definitions are related to hypothetical 1-compartment body models that don't describe most drugs in humans. Alternatively, terminal half-life (t (1/2,z)) is utilized as the single defining t (1/2) for most drugs. However, accumulation at steady state may be markedly over predicted utilizing t (1/2, z). An apparent multiple dosing half-life (t (1/2, app)) was determined from peak and trough steady-state ratios and found to be significantly less than reported terminal t (1/2)s for eight orally dosed drugs with t (1/2,z) values longer than one day. We define a new parameter, "operational multiple dosing half-life" (t (1/2, op)), as equal to the dosing interval at steady-state where the maximum concentration at steady-state is twice the maximum concentration found for the first dose. We demonstrate for diazepam that the well-accepted concept that t (1/2,z) representing the great majority of the AUC will govern accumulation can be incorrect. Using oral diazepam, we demonstrate that t (1/2, op) is remarkably sensitive to the absorption t (1/2), even when this absorption t (1/2) is much less than t (1/2,z,) and describe the relevance of this in designing extended release dosage forms. The t (1/2, op) is compared with previously proposed half-lives for predicting accumulation.
dc.language.isoen
dc.publisherSpringer/Plenum Publishers
dc.relation.isversionof10.1007/s11095-008-9787-9
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectChemistry
dc.subjectPharmacology & Pharmacy
dc.titleThe Operational Multiple Dosing Half-Life: A Key To Defining Drug Accumulation In Patients And To Designing Extended Release Dosage Forms
dc.typeinfo:eu-repo/semantics/article
dc.typeinfo:eu-repo/semantics/publishedVersion
dc.relation.journalPharmaceutical Research
dc.contributor.departmentFarmasötik Biyoteknoloji
dc.identifier.volume25
dc.identifier.issue12
dc.identifier.startpage2869
dc.identifier.endpage2877
dc.indexingWoS


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