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- Title
Cross-linked human serum albumin dimer has the potential for use as a plasma-retaining agent for the fatty acid-conjugated antidiabetic drugs.
- Authors
Taguchi, Kazuaki; Chuang, Victor Tuan Giam; Yamasaki, Keishi; Urata, Yukino; Tanaka, Ryota; Anraku, Makoto; Seo, Hakaru; Kawai, Keiichi; Maruyama, Toru; Komatsu, Teruyuki; Otagiri, Masaki
- 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.
- Subjects
HYPOGLYCEMIC agents; ALBUMINS; DIMERS; STREPTOZOTOCIN; PHARMACOKINETICS; LABORATORY rats; THERAPEUTICS
- Publication
Journal of Pharmacy & Pharmacology, 2015, Vol 67, Issue 2, p255
- ISSN
0022-3573
- Publication type
Article
- DOI
10.1111/jphp.12338