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Eur J Drug Metab Pharmacokinet ; 41(6): 839-844, 2016 Dec.
Article in English | MEDLINE | ID: mdl-26446594

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.


Subject(s)
Drugs, Chinese Herbal/pharmacokinetics , Free Radical Scavengers/pharmacokinetics , Lung/metabolism , Propionates/pharmacokinetics , Radiation-Protective Agents/pharmacokinetics , Selenium Compounds/pharmacokinetics , 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 , Female , Free Radical Scavengers/administration & dosage , Free Radical Scavengers/blood , Free Radical Scavengers/metabolism , Half-Life , Humans , Lung/pathology , Metabolic Clearance Rate , Mice, SCID , Organ Specificity , Propionates/administration & dosage , Propionates/blood , Propionates/metabolism , Radiation-Protective Agents/administration & dosage , Radiation-Protective Agents/metabolism , Selenium Compounds/administration & dosage , Selenium Compounds/blood , Selenium Compounds/metabolism , Spectrophotometry, Atomic , Tissue Distribution , Tumor Burden , Xenograft Model Antitumor Assays
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