Trial reportDrug metabolism and disposition: the biological fate of chemicals2006
Effect of milk thistle (Silybum marianum) and black cohosh (Cimicifuga racemosa) supplementation on digoxin pharmacokinetics in humans.
Trial report in Drug metabolism and disposition: the biological fate of chemicals, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 110 citations in OpenAlex.
- A Systematic Review and Classification of the Effects of P-glycoprotein Inhibitors and Inducers in Humans, Using Digoxin, Fexofenadine, and Dabigatran as Probe Drugs.Clinical pharmacokinetics · 2025Pooled it
- The effects of milk thistle (Silybum marianum) on human cytochrome P450 activity.Drug metabolism and disposition: the biological fate of chemicals · 2014Trial
- Effect of milk thistle on the pharmacokinetics of darunavir-ritonavir in HIV-infected patients.Antimicrobial agents and chemotherapy · 2012Trial
- Effect of goldenseal (Hydrastis canadensis) and kava kava (Piper methysticum) supplementation on digoxin pharmacokinetics in humans.Drug metabolism and disposition: the biological fate of chemicals · 2007Trial
- Regional absorption of talinolol mediated by intestinal transporters: insights from PBPK modeling analysis.Frontiers in pharmacology · 2026Article
- General Framework to Quantitatively Predict Pharmacokinetic Induction Drug-Drug Interactions Using In Vitro Data.Clinical pharmacokinetics · 2023Article
- Interaction between Chinese medicine and digoxin: Clinical and research update.Frontiers in pharmacology · 2023Review
- Harder, better, faster, stronger? Retrospective chart review of adverse events of interactions between adaptogens and antidepressant drugs.Frontiers in pharmacology · 2023Article
- Prediction of CYP-mediated silybin A-losartan pharmacokinetic interactions using physiological based pharmacokinetic modeling.Journal of pharmacokinetics and pharmacodynamics · 2022Article
- Herb-Drug Interactions: Worlds Intersect with the Patient at the Center.Medicines (Basel, Switzerland) · 2021Review
- Protective Effects of Silibinin onJournal of cancer prevention · 2021Article
- Ethnobotany, Phytochemistry, Traditional and Modern Uses of Actaea racemosa L. (Black cohosh): A Review.Advances in experimental medicine and biology · 2021Review
- Pharmacokinetic Interactions between Herbal Medicines and Drugs: Their Mechanisms and Clinical Relevance.Life (Basel, Switzerland) · 2020Review
- Metabolism, Transport and Drug-Drug Interactions of Silymarin.Molecules (Basel, Switzerland) · 2019Review
- Herb-drug interactions: a novel algorithm-assisted information system for pharmacokinetic drug interactions with herbal supplements in cancer treatment.European journal of clinical pharmacology · 2019Article
- Potential Influence of Centrally Acting Herbal Drugs on Transporters at the Blood-Cerebrospinal Fluid Barrier and Blood-Brain Barrier.European journal of drug metabolism and pharmacokinetics · 2018Review
- Concurrent administration of anticancer chemotherapy drug and herbal medicine on the perspective of pharmacokinetics.Journal of food and drug analysis · 2018Review
- Therapeutic Risk and Benefits of Concomitantly Using Herbal Medicines and Conventional Medicines: From the Perspectives of Evidence Based on Randomized Controlled Trials and Clinical Risk Management.Evidence-based complementary and alternative medicine : eCAM · 2017Review
- Pharmacokinetic Herb-Drug Interactions: Insight into Mechanisms and Consequences.European journal of drug metabolism and pharmacokinetics · 2016Review
- Chemoenzymatic Synthesis, Characterization, and Scale-Up of Milk Thistle Flavonolignan Glucuronides.Drug metabolism and disposition: the biological fate of chemicals · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Phytochemical-mediated modulation of P-glycoprotein (P-gp) and other drug transporters may underlie many herb-drug interactions. Serial serum concentration-time profiles of the P-gp substrate, digoxin, were used to determine whether supplementation with milk thistle or black cohosh modified P-gp activity in vivo. Sixteen healthy volunteers were randomly assigned to receive a standardized milk thistle (900 mg daily) or black cohosh (40 mg daily) supplement for 14 days, followed by a 30-day washout period. Subjects were also randomized to receive rifampin (600 mg daily, 7 days) and clarithromycin (1000 mg daily, 7 days) as positive controls for P-gp induction and inhibition, respectively. Digoxin (Lanoxicaps, 0.4 mg) was administered orally before and at the end of each supplementation and control period. Serial digoxin serum concentrations were obtained over 24 h and analyzed by chemiluminescent immunoassay. Comparisons of area under the serum concentration time curves from 0 to 3 h (AUC(0-3)), AUC(0-24), Cmax, apparent oral clearance of digoxin (CL/F), and elimination half-life were used to assess the effects of milk thistle, black cohosh, rifampin, and clarithromycin on digoxin pharmacokinetics. Rifampin produced significant reductions (p < 0.01) in AUC(0-3), AUC(0-24), and Cmax, whereas clarithromycin increased these parameters significantly (p < 0.01). Significant changes in digoxin half-life and CL/F were also observed with clarithromycin. No statistically significant effects on digoxin pharmacokinetics were observed following supplementation with either milk thistle or black cohosh, although digoxin AUC(0-3) and AUC(0-24) approached significance (p = 0.06) following milk thistle administration. When compared with rifampin and clarithromycin, supplementation with these specific formulations of milk thistle or black cohosh did not appear to affect digoxin pharmacokinetics, suggesting that these supplements are not potent modulators of P-gp in vivo.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.