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dc.contributor.authorTaguchi, K.
dc.contributor.authorChuang, Victor
dc.contributor.authorYamasaki, K.
dc.contributor.authorUrata, Y.
dc.contributor.authorTanaka, R.
dc.contributor.authorAnraku, M.
dc.contributor.authorSeo, H.
dc.contributor.authorKawai, K.
dc.contributor.authorMaruyama, T.
dc.contributor.authorKomatsu, T.
dc.contributor.authorOtagiri, M.
dc.date.accessioned2017-01-30T12:56:52Z
dc.date.available2017-01-30T12:56:52Z
dc.date.created2015-10-29T04:08:54Z
dc.date.issued2015
dc.identifier.citationTaguchi, K. and Chuang, V. and Yamasaki, K. and Urata, Y. and Tanaka, R. and Anraku, M. and Seo, H. et al. 2015. The potential of a cross-linked human serum albumin dimer in diabetic rats as an augmenting agent for antidiabetic drugs. Journal of Pharmacy and Pharmacology. 67 (2): pp. 255-263.
dc.identifier.urihttp://hdl.handle.net/20.500.11937/27086
dc.identifier.doi10.1111/jphp.12338
dc.description.abstract

Objectives The half-life of fatty acid-conjugated antidiabetic drugs are prolonged through binding to albumin, but this may not occur in diabetic patients with nephropathy complicated with hypoalbuminemia. We previously showed that human serum albumin (HSA) dimerized at the protein's Cys34 by 1,6-bis(maleimido)hexane has longer half-life than the monomer under high permeability conditions. The aim of this study was to investigate the superior ability of this HSA dimer as a plasma-retaining agent for fatty acid conjugated antidiabetic drugs. Methods The diabetic nephropathy rat model was prepared by administering a single injection of streptozotocin (STZ) intravenously, and the pharmacokinetic properties of HSA monomer and dimer were evaluated. Site-specific fluorescent probe displacement experiments were performed using warfarin and dansylsarcosine as site I and site II specific fluorescent probes, respectively. Key findings The half-life of the HSA dimer in STZ-induced diabetic nephropathy model rats was 1.5 times longer than the HSA monomer. The fluorescent probe displacement experiment results for HSA monomer and dimer were similar, where fatty acid-conjugated antidiabetic drugs displaced dansylsarcosine but not warfarin in a concentration-dependent manner. Conclusions The HSA dimer shows potential for use as a plasma-retaining agent for antidiabetic drugs due to its favourable pharmacokinetic properties.

dc.publisherBlackwell Publishing Ltd
dc.titleCross-linked human serum albumin dimer has the potential for use as a plasma-retaining agent for the fatty acid-conjugated antidiabetic drugs
dc.typeJournal Article
dcterms.source.volume67
dcterms.source.number2
dcterms.source.startPage255
dcterms.source.endPage263
dcterms.source.issn0022-3573
dcterms.source.titleJournal of Pharmacy and Pharmacology
curtin.departmentSchool of Pharmacy
curtin.accessStatusFulltext not available


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