Biodistribution and Pharmacokinetic Study of 3,3' Diseleno Dipropionic Acid (DSePA), A Synthetic Radioprotector, in Mice

Eur J Drug Metab Pharmacokinet. 2016 Dec;41(6):839-844. doi: 10.1007/s13318-015-0301-6.

Abstract

Background and objectives: 3,3' Diseleno dipropionic acid (DSePA), a synthetic compound has been shown to have radioprotective activity, especially as a lung radioprotector. In this study, the pharmacokinetics and biodistribution of DSePA in MX-1 tumour bearing SCID mice were evaluated.

Methods: Twenty SCID mice were administered DSePA (50 mg/kg bodyweight) by oral gavage following which four animals each were sacrificed at 15, 30 min, 1, 2 and 4 h. Blood and tissue samples were collected for determination of DSePA concentration by graphite furnace atomic absorption spectrometry (GFAAS) method. The control group (n = 4) was administered sterile water and sacrificed at 4 h.

Results: Peak plasma concentration (C max) of 2.7 µg/ml was observed at 15 min which returned to near baseline (baseline = 0.6 µg/ml) at 1 h following drug administration. Biphasic pharmacokinetics characterized by rapid distribution phase and a slower elimination phase were observed. Highest maximal concentration (C max) of the drug was observed in lung (19.2 µg/g at 30 min) followed by intestine (14.64 µg/g at 15 min) and kidney (12.96 µg/g at 15 min). There was negligible uptake in tumor tissue and no uptake in brain.

Conclusions: DSePA has a favorable pharmacokinetic profile which makes it a potentially good candidate for further development as a radioprotective agent.

MeSH terms

  • Administration, Oral
  • Animals
  • Area Under Curve
  • Blood-Brain Barrier / metabolism
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Drugs, Chinese Herbal / administration & dosage
  • Drugs, Chinese Herbal / metabolism
  • Drugs, Chinese Herbal / pharmacokinetics*
  • Female
  • Free Radical Scavengers / administration & dosage
  • Free Radical Scavengers / blood
  • Free Radical Scavengers / metabolism
  • Free Radical Scavengers / pharmacokinetics*
  • Half-Life
  • Humans
  • Lung / metabolism*
  • Lung / pathology
  • Metabolic Clearance Rate
  • Mice, SCID
  • Organ Specificity
  • Propionates / administration & dosage
  • Propionates / blood
  • Propionates / metabolism
  • Propionates / pharmacokinetics*
  • Radiation-Protective Agents / administration & dosage
  • Radiation-Protective Agents / metabolism
  • Radiation-Protective Agents / pharmacokinetics*
  • Selenium Compounds / administration & dosage
  • Selenium Compounds / blood
  • Selenium Compounds / metabolism
  • Selenium Compounds / pharmacokinetics*
  • Spectrophotometry, Atomic
  • Tissue Distribution
  • Tumor Burden
  • Xenograft Model Antitumor Assays

Substances

  • 3,3'-diselenodipropionic acid
  • Drugs, Chinese Herbal
  • Free Radical Scavengers
  • Propionates
  • Radiation-Protective Agents
  • Selenium Compounds