TABLE 2

Metabolism of ADT with microsomes from insect cells expressing various recombinant human CYP and FMO enzymes (Supersomes)

Percentage of ADT or metabolite yields ± S.D. from two to four experiments, from 100 μM ADT after 2 hours of incubation in the presence of 0.2 μM recombinant CYP enzymes or from 1 hour of incubations containing 1 mg/ml recombinant FMO. Quantitation of ADT and of its metabolites was performed by integration of UV-visible spectra using calibration curves as described in Materials and Methods.

EnzymeADTdmADTADTSOADOdmADOpMA
CYP1A136 ± 258 ± 5ND8 ± 22 ± 11 ± 1
CYP1A218 ± 275 ± 5ND3 ± 24 ± 21 ± 1
CYP1B122 ± 474 ± 5ND3 ± 21 ± 1ND
CYP2A693 ± 6NDND6 ± 2NDND
CYP2C973 ± 623 ± 4ND3 ± 21 ± 1ND
CYP2C1921 ± 475 ± 6ND3 ± 11 ± 1ND
CYP2D648 ± 516 ± 4ND28 ± 4ND6 ± 2
CYP2E144 ± 535 ± 5ND7 ± 28 ± 34 ± 2
CYP3A447 ± 5NDND40 ± 5ND13 ± 4
FMO172 ± 6ND4 ± 216 ± 4ND6 ± 2
FMO393 ± 5ND4 ± 23 ± 1NDND
  • ADO, 5-(p-methoxyphenyl)-3H-1,2-dithiole-3-one; ADT, 5-(p-methoxyphenyl)-3H-1,2-dithiole-3-thione; ADTSO, 5-(p-methoxyphenyl)-3H-1,2-dithiole-3-thione sulfoxide; dmADO, 5-(p-hydroxyphenyl)-3H-1,2-dithiole-3-one; dmADT, 5-(p-hydroxyphenyl)-3H-1,2-dithiole-3-thione; ND, not detected; pMA, 4-methoxy-acetophenone.