Aucun titre de diapositive

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
DADSO
4
Km nmole
Vmax nmol/min/mg prt
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
6.18 0.23
11.00 1.67
n.d.
AGS
0.21 0.01
0.21 0.01
n.d.
?
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
Total Ionic Current chromatogram of the extract
of liver, perfused with DADS, obtained on
GC-MS.
8
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 ?