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In vitro metabolism of DADS by rat and human subcellular fractions

In vitro metabolism of DADS by rat and human subcellular fractions. Results in rat presented Results in human similar with the same metabolites. In vitro metabolism of DADS in rat. DADS. cofactors. ultracentrifugation. HPLC-UV. microsomes cytosols. subcellular fractions. AM

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In vitro metabolism of DADS by rat and human subcellular fractions

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  1. In vitro metabolism of DADS by rat and human subcellular fractions Results in rat presented Results in human similar with the same metabolites

  2. In vitro metabolism of DADS in rat DADS cofactors ultracentrifugation HPLC-UV microsomes cytosols subcellular fractions

  3. AM allyl mercaptan GST DADS AGS allyl glutathionyl sulfide CYP 2B1/2 CYP 2E1 FMO DADSO

  4. Vmax nmol/min/mg prt Km nmole Vmax/Km products DADSO 0.86 ± 0.12 0.47 ± 0.12 1.83 AGS + AM 9.03 ± 2.56 0.25 ± 0.04 0.03  DADS  DADSO monooxigenase nmol/min/mg prt GST nmol/min/mg prt monooxygenase + GST nmol/min/mg prt products DADSO 1.82 ± 0.20 n.d. n.d. AM n.d. 6.18 ± 0.23 11.00 ± 1.67 AGS n.d. 0.21 ± 0.01 0.21 ± 0.01  DADS  DADSO + AM + AGS

  5. Isolated rat perfused liver liver collected bile

  6. Single dose pharmacokinetic parameters for DADS in an isolated perfused rat liver. kel (min-1) 0.13 ± 0.03 AUC0- (min.mmol/l) 4.77 ± 0.80 t1/2 (min) 6.09 ± 1.26 Clearance (ml/min) 34.22 ± 5.6 Volume of distribution (ml) 311.9 ± 0.08

  7. nonane 60000 11.34 55000 AMSO2 50000 25.61 45000 AMS p- Cymène 40000 6.15 17.64 35000 AMSO 30000 22.56 25000 20000 15000 DADS AM 10000 20.72 3.66 5000 0 4 6 8 10 12 14 16 18 20 22 24 26 Time (min) Total Ionic Current chromatogram of the extract of liver, perfused with DADS, obtained on GC-MS.

  8. MT CYP 2B1/2 CYP 2E1 FMO Compounds obtained in presence of subcellular fractions Compounds obtained in an isolated perfused liver AMSO2 allyl methyl sulfone AMSO allyl methyl sulfoxide AMS allyl methyl sulfide DADS AM allyl mercaptan GST AGS allyl glutathionyl sulfide DADSO

  9. DADS: short half live time many metabolites  Which is the real active molecule in vivo ?

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