Selective P450 chemical inhibition of abrocitinib metabolism in pooled human hepatocytes and overall fractional P450 pathway assignment (fm)
| Metabolite | fCL | % P450 Inhibition (Scaled) | P450 Pathway fm | ||||||
|---|---|---|---|---|---|---|---|---|---|
| 2B6 | 2C9 | 2C19 | 3A4 | 2B6 | 2C9 | 2C19 | 3A4 | ||
| M1 (M7) | 0.41 | 16 | 24 | 52 | 8.0 | 0.066 | 0.10 | 0.22 | 0.033 |
| M2/M3 | 0.29 | 44 | 55 | 0.13 | 0.16 | ||||
| M4 (358-1, 372-1) | 0.27 | 25 | 57 | 18 | 0.067 | 0.15 | 0.048 | ||
| 149 | 0.029 | 100 | 0.030 | ||||||
| Overall fm | 0.066 | 0.30 | 0.53 | 0.11 | |||||
Nonstatistical contributions by the remaining P450 isoforms for M1 (1A2, 2C8, 2D6), M2/M3 (1A2, 2B6, 2C8, 2D6, 3A), M4 (1A2, 2B6, 2C8, 2D6), and 149 (1A2, 2B6, 2C8, 2C9, 2C19, 2D6) were observed and excluded from fraction metabolized determinations. Fraction metabolized was calculated as the product of fCL and fraction inhibited (scaled) as described in eq. 7.