Clinical Pharmacokinetics and Metabolism of Berberine and Hydrastine Following an Oral Dose of Goldenseal Supplement

To determine the pharmacokinetics and metabolism of hydrastine and berberine in human subjects after an oral dose of goldenseal supplement. Subjects (n=11) were given a single dose of goldenseal supplement (2.7g) and 78mg hydrastine and 132mg berberine. Serial serum (48h) and urine samples were collected to assess the serum kinetics and urinary excretion. Hydrastine and berberine concentrations were determined using HPLC-MS/MS methodology. Metabolites of hydrastine and berberine were identified using liquid chromatography coupled to high-resolution mass spectrometry. (LC-QToF). Pharmacokinetic parameters were calculated from serum concentration-time profiles using a model-independent approach. For hydrastine, maximal serum concentration (C_max) was 225±100ng/ml, the time at which it occurred (t_max) was 1.5±0.3h, and AUC was 6.4±4.1ng*h/ml*kg. The elimination half-life was 4.8±1.4h. Corresponding values for berberine were 1.1±1.2ng/ml, 3.0±3.3h and 0.15±0.09ng*h/ml*kg, respectively. A berberine elimination phase was not evident from the serum concentration-time profile. Qualitative assessment of serum and urine showed rapid phase I and phase II metabolism of hydrastine and berberine. Phase I metabolites of hydrastine were found to undergo glucuronidation but not sulfation, while phase I metabolites of berberine were preferentially sulfated. The identity of different phase I and phase II metabolites was further confirmed by accurate mass measurement (<5 ppm). Hydrastine and berberine absorption was extensive following oral administration of goldenseal supplement. Hydrastine serum AUC was considerably higher than that of berberine suggesting that hydrastine bioavailability was higher than berberine. Berberine serum and urine concentrations suggested enterohepatic recycling of berberine and a high volume of distribution for berberine.