Fractional bioactivation and computational scores for each observed meclofenamate metabolite and corresponding adduct
| Analyte | Model Scorea | Depletion Vmax/Km | Bioactivation Vmax/Km or Kh | Fbab | Bioactivation (%) |
|---|---|---|---|---|---|
| Dechloro-ortho-quinone-imine | 0.26 | 3.8 (3.1–4.6) | 0.053 (0.031–0.090) | 5.3 (3.1–9.0) | |
| Monohydroxy para-quinone-imine | 0.67/0.92c | 5.0 (3.4–7.5) | 0.070 (0.034–0.147) | 7.0 (3.4–14.7) | |
| Dihydroxy ortho-quinone | 0.42/0.45c | 0.12 (0.08–0.19) | 0.002 (0.001–0.004) | 0.2 (0.1–0.4) | |
| Multi-GSH adduct | NPd | 0.18 (0.12–0.27) | 0.003 (0.001–0.005) | 0.3 (0.1–0.5) | |
| Total | 71.1 (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.