Fractional bioactivation and computational scores for each observed meclofenamate metabolite and corresponding adduct

AnalyteModel ScoreaDepletion Vmax/KmBioactivation Vmax/Km or KhFbabBioactivation (%)
Dechloro-ortho-quinone-imine0.263.8 (3.1–4.6)0.053 (0.031–0.090)5.3 (3.1–9.0)
Monohydroxy para-quinone-imine0.67/0.92c5.0 (3.4–7.5)0.070 (0.034–0.147)7.0 (3.4–14.7)
Dihydroxy ortho-quinone0.42/0.45c0.12 (0.08–0.19)0.002 (0.001–0.004)0.2 (0.1–0.4)
Multi-GSH adductNPd0.18 (0.12–0.27)0.003 (0.001–0.005)0.3 (0.1–0.5)
Total71.1 (51.0–99.2)9.1 (6.7–12.6)0.128 (0.067–0.246)12.8 (6.7–24.6)
  • a Model scores reflect the relative likelihood for metabolite formation after metabolism of the parent drug, meclofenamate. Scores range from 0.0 to 1.0, with higher scores indicating a greater likelihood for formation of the specific metabolite structure.

  • b Fractional bioactivation (Fba) is defined as a fraction of metabolic bioactivation catalytic efficiency and metabolic depletion catalytic efficiency.

  • c Multiple bioactivation scores reflect different possible reactive metabolite isomers whose structures could not be definitively attributed to the observed metabolite based on mass spectrometry.

  • d No prediction (NP) for putative metabolite and adduct because of the inability to characterize its structure by mass spectrometry.