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.

InhibitorInhibited EnzymeKI (μM)kinact (min−1)kinact/KIa (mM−1 min−1)
BerberineCYP2D62.68 ± 0.260.065 ± 0.00624.3
BerberineCYP3A4/514.8 ± 2.60.019 ± 0.0051.3
(−)-β-HydrastineCYP2C949 ± 160.036 ± 0.0070.7
(−)-β-HydrastineCYP2D6>250>0.06<0.2
(−)-β-HydrastineCYP3A4/528 ± 120.056 ± 0.0052.0
HydrastinineCYP2D637 ± 130.049 ± 0.0093.8
  • 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).