Goldenseal (Hydrastis canadensis) 43525850
Supplementation With Goldenseal (Hydrastis canadensis), but not Kava Kava (Piper methysticum), Inhibits Human CYP3A Activity In Vivo CSV JSON

The effects of goldenseal (Hydrastis canadensis) and kava kava (Piper methysticum) supplementation on human CYP3A activity were evaluated using midazolam (MDZ) as a phenotypic probe. Sixteen healthy volunteers were randomly assigned to receive either goldenseal or kava kava for 14 days. Each supplementation phase was followed by a 30-day washout period. MDZ (8 mg, per os) was administered before and after each phase, and pharmacokinetic parameters were determined using standard non-compartmental methods. Comparisons of pre- and post-supplementation MDZ pharmacokinetic parameters revealed significant inhibition of CYP3A by goldenseal (AUC(0–N), 107.9743.3 vs 175.3774.8 ng x h/ml; Cl/F/kg, 1.2670.59 vs 0.8170.45 l/h/kg; T1/2, 2.0170.42 vs 3.1571.12 h; Cmax, 50.6726.9 vs 71.2750.5 ng/ml). MDZ disposition was not affected by kava kava supplementation. These findings suggest that significant herb–drug interactions may result from the concomitant ingestion of goldenseal and CYP3A substrates.

PMID: 17495878

17495878

1 . CYP3A4 Experiment - MDZ probe (id=NPDI-Aw3yIw)

In Vivo Interaction Study

Increased systemic exposure was detected.

midazolam 708298

  • CYP3A4 4306811

Results

Control is pre-goldenseal administration 
Test is post-goldenseal administration
Data from Table 1/Table 2

Sample Compound measured Value Measurement Study sequence Additional information N replicates

Experimental Conditions

Multiple dosing

Population

Females
Males

Nonsmokers

16

8 women. 

Normal diet, and were not users of botanical dietary supplements; nor were they taking any prescription medications. All female subjects had a negative pregnancy test at baseline, and

Pharmacokinetic (PK) Sampling Information

0, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, and 6 h

Drug or Natural Product Administration

Object Administration — midazolam

Oral

Unspecified

8 mg with 240 mL of water

14 days administered 24h before the start of each supplementation/medication phase (baseline) and again on the last day of each phase.

Precipitant Administration — goldenseal root extract

Oral

Capsule

3969 mg

three times daily

14 days

Natural Product Characteristics

Nautre’s Resource Products

not specified

standardized to contain 24.1 mg isoquinoline alkaloids per capsule