Preliminary results indicate that, in the absence of pre-treatment with NADPH (-NADPH), berberine is a moderate, reversible inhibitor of CYP2D6 (IC50, 9.9 μM). However, following pre-treatment with NADPH (+NADPH), an IC50 shift of 6-fold was observed, reducing the IC50 to 1.6 μM, indicating substantial time-dependent inhibition. Berberine did not affect CYP2C9 activity but appeared to both reversibly activate and irreversibly inactivate CYP3A4.
In vitro to in vivo extrapolation (IVIVE)
Placing the preliminary IC50 values into context, plasma concentrations of berberine in humans after administration of goldenseal extracts are in the 10 nM range, whereas 100-fold higher concentrations of hydrastine have been reported.1
Healthy volunteers (8 men and 8 non-pregnant, non-lactating women), aged 18-65 years and of any race/ethnicity, were recruited to participate in an open-label, crossover, fixed-sequence goldenseal-drug interaction study. The control (baseline) phase consists of administration of an oral probe drug cocktail consisting of midazolam, furosemide, metformin, and rosuvastatin. The treatment phase consists of administration of a well-characterized oral goldenseal product three times daily for one week, followed by administration of the oral drug cocktail with the goldenseal product. Each phase was separated by at least one week to ensure sufficient washout of the probe drugs.
Results of the clinical goldenseal-drug interaction study coming soon from the Pharmacology Core…
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