Vikram Gota1, Jayant S Goda2, Kartik Doshi3, Anand Patil3, Suvarna Sunderajan4, Kiran Kumar4, Mahendra Varne5, Amit Kunwar5, Vimal Kumar Jain6, Indira Priyadarshini5. 1. Department of Clinical Pharmacology, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai, 410210, India. vgota76@gmail.com. 2. Department of Radiation Oncology, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai, India. 3. Department of Clinical Pharmacology, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai, 410210, India. 4. Analytical Chemistry Division, Bhabha Atomic Research Centre, Mumbai, India. 5. Radiation and Photochemistry Division, Bhabha Atomic Research Centre, Mumbai, India. 6. Chemistry Division, Bhabha Atomic Research Centre, Mumbai, India.
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.
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 SCIDmice 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.
Authors: Amit Kunwar; P Bansal; S Jaya Kumar; P P Bag; P Paul; N D Reddy; L B Kumbhare; V K Jain; R C Chaubey; M K Unnikrishnan; K I Priyadarsini Journal: Free Radic Biol Med Date: 2009-11-18 Impact factor: 7.376