A herb-drug interactions through evaluating cytochrome P450 phenotypic ratios after multiple administration of herbal supplements

Objectives This study was to investigate the effect of three herbal supplements(Ephedra sinica(Ma-huang), Scutellaria baicalensis-(Baical Skullcap), Aconitum carmichaeli(Aconite)) popular in Korea on the Cytochrome P450(CYP) activities. A cocktail approach was used to determine if multiple administration of herbal supplements affects CYP1A2, CYP2D6, CYP2E1, CYP3A4 activities. Methods Twenty four healthy male subjects were randomly allocated to receive Ma-huang, Baical Skullcap, Aconite or Hypericum perforatum (St. John's wort, SJW) for 12 days respectively. Probe drugs for CYP1A2, CYP2D6, CYP2E1, CYP3A4 were caffeine, dextromethorphan, chlorzoxazone and midazolam. Phenotyping was done by measuring paraxanthine/caffeine plasma ratio(6 hour after administrated) for CYP1A2, dextrophan/dextromethorphan urine recovery ratio for CYP2D6(0-12 hour collection), 6-hydroxychlorzoxazone/chlorzoxazone plasma ratio(2 hour) for CYP2E1, 1–hydroxymidazolam/midazolam plasma ratio(1, 2, 6 hour) for CYP3A4. Results Comparisons of Pre- and post-supplementation phenotyping results showed that Aconite inhibited CYP2E1 activity by 50%(P=0.0016). Baical Skullcap showed trends to inhibit CYP1A2 activity (P=0.0731). Conclusions Aconite might be a potent CYP2E1 inhibitor. The presence of herbs as supplementary medicines in Korea could cause a potential of herb-drug interactions, therefore, a cocktail approach might provide useful means for screening potential herb-drug interactions. Clinical Pharmacology & Therapeutics (2004) 75, P80–P80; doi: 10.1016/j.clpt.2003.11.305