An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected commercial herbal extracts and tinctures

Budzinski, J.W.; Foster, Brian; Vandenhoek, S.; Arnason, John T.

doi:10.1016/s0944-7113(00)80044-6

Cited by 321 publications

(242 citation statements)

References 16 publications

Supporting

Mentioning

223

Contrasting

Unclassified

Order By: Relevance

“…We have previously investigated the in vitro inhibition of CYP3A4 by various commercial herbal tinctures (Budzinski et al, 2000) and numerous other herbal preparations (Foster et al, 2002Awad et al, 2003;Scott et al, 2006), and have made preliminary in vitro investigations of the P-gp ATPase activity and substrate efflux of selected herbals such as garlic, St. John's wort, and African potato (Foster et al, 2001(Foster et al, , 2004Nair et al, 2007). The goal of this study was to determine if selected (Table 1) commercially available teas and capsule preparations of several popular herbal NHPs used by the HIV+ community (CATIE, 2005;Lee et al, 2006), related phytochemicals, and a few HIV drugs could inhibit CYP3A4-mediated metabolism of a reference substrate and stimulate P-gp ATPase activity.…”

Section: Introductionmentioning

confidence: 99%

The Interaction of Selected Phytochemicals, HIV Drugs, and Commercial-Source Herbal Teas and Capsules with Human Cytochrome P450 3A4 and P-glycoprotein

Budzinski

Foster

Trudeau

et al. 2008

Pharmaceutical Biology

View full text Add to dashboard Cite

As the popularity of natural health product (NHP) use increases, unfortunately, so does the frequency of cases reporting suspected adverse interactions. Adverse reactions associated with concomitant NHP-therapeutic use may result from competing interactions at the level of the key xenobiotic-biotransforming phase I enzyme cytochrome P450 3A4 (CYP3A4) or the membrane-bound ATP-dependent protein pump P-glycoprotein (P-gp). In this study, selected NHPs of interest to the HIV+ community were assessed for their ability to affect these two important mechanisms of drug disposition. Briefly, commercial-source teas and powdered extracts in capsule formulations were examined for their ability to inhibit CYP3A4-mediated metabolism of the coadministered reference substrate dibenzyl-fluorescein, and their ability to stimulate P-gp ATPase activity. Among the herbal capsules, it was found that aqueous extracts of two different goldenseal (Hydrastis canadensis L.) products were the most inhibitory of CYP3A4-mediated metabolism among all NHPs tested (IC 50 : 3.03 and 3.23 mg/mL). Goldenseal and milk thistle [Silybum marianum (L.) Gaertn.] teas were found to stimulate P-gp ATPase to a greater degree than the reference positive control verapamil (20 µM). As well, 70% ethanol extracts of one goldenseal product (designated NRP 121) and aqueous extracts of another (designated NRP 17) had the highest relative P-gp ATPase activity overall. Milk thistle and goldenseal products were further analyzed * Dedicated to Professor John Thor Arnason of the University of Ottawa, Department of Biology, on the occasion of his sixtieth birthday.

show abstract

Section: Introductionmentioning

confidence: 99%

The Interaction of Selected Phytochemicals, HIV Drugs, and Commercial-Source Herbal Teas and Capsules with Human Cytochrome P450 3A4 and P-glycoprotein

Budzinski

Foster

Trudeau

et al. 2008

Pharmaceutical Biology

View full text Add to dashboard Cite

show abstract

“…During the past decade, several potential mechanisms of interactions of valerian preparations, involving CYP enzymes, P-glycoprotein, and UGTs, have been studied in vitro [36,[38][39][40][41][42]46]. Some of these studies pointed to a possible drug interaction potential by valerian extracts.…”

Section: Discussionmentioning

confidence: 99%

“…Budzinski et al [38] used a fluorometric assay for analysis of the in vitro CYP 3A4 inhibitory capability of dilutions of a valerian fluid extract (no further information available) using human CYP 3A4. An IC 50 of 1.8% the undiluted extract in the reaction mixture was identified.…”

Section: In Vitro Studiesmentioning

confidence: 99%

Valerian: No evidence for Clinically Relevant interactions

Kelber¹,

Nieber²,

Kraft³

2012

Planta Med

View full text Add to dashboard Cite

In recent popular publications as well as in widely used information websites directed to cancer patients, valerian is claimed to have a potential of adverse interactions with anticancer drugs. This questions its use as a safe replacement for, for example, benzodiazepines. A review on the interaction potential of preparations from valerian root (Valeriana officinalis L. root) was therefore conducted. A data base search and search in a clinical drug interaction data base were conducted. Thereafter, a systematic assessment of publications was performed. Seven in vitro studies on six CYP 450 isoenzymes, on p-glycoprotein, and on two UGT isoenzymes were identified. However, the methodological assessment of these studies did not support their suitability for the prediction of clinically relevant interactions. In addition, clinical studies on various valerian preparations did not reveal any relevant interaction potential concerning CYP 1A2, 2D6, 2E1, and 3A4. Available animal and human pharmacodynamic studies did not verify any interaction potential. The interaction potential of valerian preparations therefore seems to be low and thereby without clinical relevance. We conclude that there is no specific evidence questioning their safety, also in cancer patients.

show abstract

“…These results may not agree with in vivo studies because human liver microsomes are not able to predict enzyme induction due to inability of microsomal preparations to synthesize new proteins thus may not give an indication of potential induction in vivo. An example of this is the case of St John's Wort which has been shown to induce both CYP3A4 through an action on PXR in vivo, as well as Pgp and CYP2C19 but in vitro, it inhibits CYP2D6, CYP 2C9 and CYP3A4 (110,111).…”

Section: Investigating Herb-drug Interactionmentioning

confidence: 99%

Pharmacokinetics and Drug Interactions of Herbal Medicines: A Missing Critical Step in the Phytomedicine/Drug Development Process

Obodozie¹

2012

Readings in Advanced Pharmacokinetics - Theory, Methods and Applications

View full text Add to dashboard Cite

An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected commercial herbal extracts and tinctures

Cited by 321 publications

References 16 publications

The Interaction of Selected Phytochemicals, HIV Drugs, and Commercial-Source Herbal Teas and Capsules with Human Cytochrome P450 3A4 and P-glycoprotein

The Interaction of Selected Phytochemicals, HIV Drugs, and Commercial-Source Herbal Teas and Capsules with Human Cytochrome P450 3A4 and P-glycoprotein

Valerian: No evidence for Clinically Relevant interactions

Pharmacokinetics and Drug Interactions of Herbal Medicines: A Missing Critical Step in the Phytomedicine/Drug Development Process

Contact Info

Product

Resources

About