Goldenseal (Hydrastis canadensis)
Influence of Goldenseal Root on the Pharmacokinetics of Indinavir
Goldenseal root was identified as the most potent inhibitor of CYP3A4 in a study that tested 21 popular herbal products for in vitro inhibitory activity. The purpose of this investigation was to examine the influence of goldenseal root on the dispo- sition of the CYP3A4 substrate indinavir in humans. Using a crossover study design, the pharmacokinetics of indinavir were characterized in 10 healthy volunteers before and after 14 days of treatment with goldenseal root (1140 mg twice daily). Indinavir was given as a single 800-mg oral dose, and blood samples were collected for 8 hours following the dose. No statistically significant differences in peak concentration (11.6 vs. 11.9 mg/L) or oral clearance (26.8 vs. 23.9 mg•h/L) were observed following treatment with goldenseal root. Half-life and time to reach peak concentration were also un- changed by goldenseal. These results suggest that patients being treated with indinavir can safely take goldenseal root and that interactions with other drugs metabolized by CYP3A4 in the liver are unlikely.
In Vivo Interaction Study
No Effect (based on bioequivalence limits) was detected.
- CYP3A4 4306811
Converted Cmax from mg/L (in study) to ng/mL (shown above)
|Sample||Compound measured||Value||Measurement||Study sequence||Additional information||N replicates|
Indinavir was administered on an empty stomach with 200 mL tap water following an overnight fast.
A standard lunch (ham or turkey sandwich, potato salad, coleslaw, soft drink) was served following the 4-hour blood sample.
Eleven nonsmoking healthy subjects (6 males, 5 females) within 15% of ideal body weight and ranging in age from 21 to 47 years (mean 25.5 years) provided written informed consent and participated in the study. Subjects had no history of any chronic disease known to affect the metabolism and elimination of drugs. In addition, they did not take any prescription, over-the-counter, or herbal medicine known to influ- ence CYP3A4 activity for at least 1 month prior to the start of the study and were prohibited from taking these products throughout the study period. The study was approved by the Wayne State University Human Investigation Committee.
0, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, and 8.0 hours
Drug or Natural Product Administration
Two doses administered at beginning and end of two weeks
Two times daily without regard to meals; final dose taken 30 min prior to the administration of indinavir
Nature’s Way, Springville, UT