ArticlePharmaceutical research2000
Dextran-methylprednisolone succinate as a prodrug of methylprednisolone: immunosuppressive effects after in vivo administration to rats.
Article in Pharmaceutical research, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 15 citations in OpenAlex.
- Hepatic immunosuppressive effects of systemically administered novel dextran-methylprednisolone prodrugs with peptide linkers in rats.Journal of pharmaceutical sciences · 2012Article
- Plasma pharmacokinetics and tissue disposition of novel dextran-methylprednisolone conjugates with peptide linkers in rats.Journal of pharmaceutical sciences · 2010Article
- Liquid chromatography-tandem mass spectrometry for the determination of methylprednisolone in rat plasma and liver after intravenous administration of its liver-targeted dextran prodrug.Journal of chromatography. B, Analytical technologies in the biomedical and life sciences · 2009Article
- Synthesis and in vitro characterization of novel dextran-methylprednisolone conjugates with peptide linkers: effects of linker length on hydrolytic and enzymatic release of methylprednisolone and its peptidyl intermediates.Journal of pharmaceutical sciences · 2008Article
- Attenuation of acute rejection in a rat liver transplantation model by a liver-targeted dextran prodrug of methylprednisolone.Transplantation · 2006Article
- Attenuation of Kupffer cell activation in cold-preserved livers after pretreatment of rats with methylprednisolone or its macromolecular prodrug.Pharmaceutical research · 2003Article
- Dextran-methylprednisolone succinate as a prodrug of methylprednisolone: local immunosuppressive effects in liver after systemic administration to rats.Pharmaceutical research · 2003Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
purposeTo study the immunosuppressive activities of a macromolecular prodrug of methylprednisolone (MP), dextran-methylprednisolone succinate (DEX-MPS), in rats.
methodsSingle 5 mg/kg (MP equivalent) doses of MP or DEX-MPS were administered intravenously to rats, and blood and spleen samples were collected over 96 h. The immunosuppressive activity was determined by the effects of the free or dextran-conjugated drug on the mitogen-stimulated spleen lymphocyte proliferation. Additionally, the number of lymphocytes in the spleen cell suspensions was estimated. Further, the plasma and spleen concentrations of the conjugated and free MP were determined using size-exclusion and reversed-phase chromatographic methods, respectively.
resultsBoth MP and DEX-MPS injections resulted in the inhibition of the spleen lymphocyte proliferation. However, the maximal effect of DEX-MPS was significantly (P < 0.003) more intense (approximately 100% inhibition) and delayed (24 h) relative to that of MP (approximately 50% inhibition at 2 h). The DEX-MPS injection also resulted in a significantly (P < 0.0001) higher decline in the estimated number of spleen lymphocytes (approximately 80% at 24 h), compared with the MP injection (approximately 30% at 2 hr). Whereas the plasma and spleen concentrations of MP could not be measured at > or = 2 h after the drug injection, relatively high concentrations of DEX-MPS persisted in plasma and spleen for 24 h and 96 h, respectively.
conclusionDextran-methylprednisolone conjugate can effectively deliver the corticosteroid to its site of action for immunosuppression, resulting in more intense and sustained effects when compared with the free drug administration.
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