TABLE 2.
Kinetic parameters for the inactivation of CYP2C9, CYP2D6, and CYP3A4/5 in HLMs by goldenseal component alkaloids
Values denote means ± S.D. of three separate experiments.
| Inhibitor | Inhibited Enzyme | KI (μM) | kinact (min−1) | kinact/KIa (mM−1 min−1) |
|---|---|---|---|---|
| Berberine | CYP2D6 | 2.68 ± 0.26 | 0.065 ± 0.006 | 24.3 |
| Berberine | CYP3A4/5 | 14.8 ± 2.6 | 0.019 ± 0.005 | 1.3 |
| (−)-β-Hydrastine | CYP2C9 | 49 ± 16 | 0.036 ± 0.007 | 0.7 |
| (−)-β-Hydrastine | CYP2D6 | >250 | >0.06 | <0.2 |
| (−)-β-Hydrastine | CYP3A4/5 | 28 ± 12 | 0.056 ± 0.005 | 2.0 |
| Hydrastinine | CYP2D6 | 37 ± 13 | 0.049 ± 0.009 | 3.8 |
a
Reported kinact/KI values (mM−1 min−1) for the TDI of specific P450 activities, in either HLMs (paroxetine, troleandomycin) or human hepatocytes (tienilic acid), for clinically relevant time-dependent inhibitors: tienilic acid (CYP2C9) = 25; paroxetine (CYP2D6) = 35; and troleandomycin (CYP3A4/5) = 13.3 (Bertelsen et al., 2003; Zhao et al., 2005; McGinnity et al., 2006).