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Dextran sulfate disposition in the rat.

B C Foster1, K D Gallicano, L W Whitehouse

  • 1Bureau of Drug Research, Ottawa, Ontario, Canada.

Biopharmaceutics & Drug Disposition
|October 1, 1990
PubMed
Summary
This summary is machine-generated.

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Oral administration of dextran sulfate in rats leads to rapid metabolism into smaller molecules before systemic absorption. Intravenous dosing results in direct excretion, while oral dosing shows significant fecal loss and altered distribution patterns.

Area of Science:

  • Pharmacokinetics and Drug Metabolism
  • Biochemistry and Molecular Biology

Background:

  • Understanding the absorption, distribution, metabolism, and excretion (ADME) of dextran sulfate is crucial for its therapeutic applications.
  • Previous studies have not fully elucidated the disposition of orally administered dextran sulfate.

Purpose of the Study:

  • To compare the distribution patterns of tritiated dextran sulfate following oral versus intravenous administration in rats.
  • To investigate the metabolic fate and systemic bioavailability of orally administered dextran sulfate.

Main Methods:

  • Rats were administered tritiated dextran sulfate orally or intravenously.
  • Radioactivity was quantified in feces and urine over 24 hours.
  • Plasma and urine samples were analyzed using Sephadex column chromatography.

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Main Results:

  • Intravenous dosing led to rapid urinary excretion of intact dextran sulfate.
  • Oral dosing resulted in lower recovery in feces and urine, with significant unabsorbed drug in feces.
  • Orally absorbed dextran sulfate appeared to be rapidly metabolized to low molecular weight products before entering systemic circulation.

Conclusions:

  • Oral administration of dextran sulfate results in significant pre-systemic metabolism.
  • The disposition of orally administered dextran sulfate differs markedly from intravenous administration due to extensive metabolism.
  • Further research is needed to fully characterize the metabolic pathways and distribution of these metabolites.