Superior Plasma Retention of a Cross-Linked Human Serum Albumin Dimer in Nephrotic Rats as a New Type of Plasma Expander
| Autor: | Eishun Tsuchida, Toru Maruyama, Teruyuki Komatsu, Masaki Otagiri, Kazuaki Taguchi, Makoto Anraku, Yukino Urata, Hiroshi Watanabe, Keiichi Kawai |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Male
medicine.medical_specialty Nephrotic Syndrome Dimer Nephrosis Blotting Western Plasma Substitutes Serum albumin Pharmaceutical Science Rats Sprague-Dawley chemistry.chemical_compound Internal medicine Blood plasma medicine Animals Serum Albumin Pharmacology Chromatography biology Albumin medicine.disease Human serum albumin Rats body regions Endocrinology chemistry Renal physiology embryonic structures biology.protein Protein Multimerization Nephrotic syndrome Half-Life medicine.drug |
| Zdroj: | Drug Metabolism and Disposition. 38:2124-2129 |
| ISSN: | 1521-009X 0090-9556 |
| DOI: | 10.1124/dmd.109.031989 |
| Popis: | Human serum albumin (HSA) is used clinically as a plasma expander in patients with hypoalbuminemia and can also function as a drug carrier. However, the administered HSA is readily eliminated from the blood circulation under pathological conditions, especially the nephrotic syndrome. In this study, we present data on the pharmacokinetics of a structurally defined HSA dimer [two HSA molecules that are cross-linked by reaction with 1,6-bis(maleimido)hexane via Cys34] in nephrotic rats and its superior circulation persistence, owing to the molecular size effect. The half-time (t(1/2)) of the HSA dimer persisted in the circulation 1.3 times longer than that of monomeric HSA in normal rats, primarily because of the suppression of the accumulation of the HSA dimer in the skin and muscle. In nephrotic rats, the t(1/2) of the HSA monomer decreased considerably, whereas the HSA dimer remained unaltered in the blood stream, similar to that for normal rats. As a result, the t(1/2) of the HSA dimer was 2-fold longer than that of the HSA monomer. This longer t(1/2) can be attributed to the fact that accumulation in the kidney and urinary excretion of the HSA dimer were significantly suppressed. The cross-linked HSA dimer shows a longer blood circulation than native HSA monomer in nephrotic rats, which can be attributed to the suppression of renal filtration and leakage into the extravascular space. This HSA dimer has the potential for use as a drug carrier, new plasma expander, and an artificial albumin-based oxygen carrier under a high glomerular permeability condition such as nephrosis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|