Planta Med 2012; 78(13): 1458-1477
DOI: 10.1055/s-0032-1315117
Mechanism of Herb-Drug Interactions
Reviews
Georg Thieme Verlag KG Stuttgart · New York

Clinical Evidence of Herbal Drugs As Perpetrators of Pharmacokinetic Drug Interactions

Robert Hermann
1   Clinical Research Appliance, Radolfzell, Germany
,
Oliver von Richter
2   Merck Serono, Darmstadt, Germany
› Institutsangaben
Weitere Informationen

Publikationsverlauf

received 28. Februar 2012
revised 22. Juni 2012

accepted 02. Juli 2012

Publikationsdatum:
01. August 2012 (online)

Abstract

The use of herbal/botanical products, also referred to as complementary and alternative medicines (CAM), worldwide enjoys increasing popularity. It appears in particular highly prevalent in patient populations already exposed to complex treatment algorithms and polypharmacotherapy, frequently involving narrow therapeutic index drugs. Accordingly, the potential clinical dimension and relevance of herb-drug interactions has received considerable attention over the last years. However, review of pertinent literature indicates that the available clinical evidence in this regard is still limited and sometimes inconclusive. Also, communication of herb-drug interaction data in the biopharmaceutical/medical literature is often complex and confusing, not always unbiased, and in many cases appears not to strive for clear-cut and useful guidance in terms of the clinical relevance of such findings.

This systematic review summarizes and interprets the published evidence on clinical herb-drug interaction studies which examined the potential of six popular herbal drugs (Echinacea, garlic, gingko, ginseng, goldenseal, and milk thistle) as perpetrators of pharmacokinetic (PK) drug interactions. Reported effect sizes were systematically categorized according to FDA drug interaction guideline criteria. A total of 66 clinical PK interaction studies, meeting the scope of the present review, were identified. The clinical evidence was found to be most robust and informative for Gingko biloba (GB; 21 studies) and milk thistle/silymarin (MT; 13), and appears still limited for ginseng (9), goldenseal/berberine (GS; 8), garlic (8), and Echinacea (7). Collectively, the available evidence indicates that, at commonly recommended doses, none of these herbs act as potent or moderate inhibitors or inducers of cytochrome P450 (CYP) enzymes or P-glycoprotein (ABCB1). Weak effects in terms of either induction or inhibition were found for GB (presystemic/hepatic CYP3A4 induction/inhibition, CYP2C19 induction at high doses), milk thistle/silymarin (CYP2C9 inhibition), GS/berberine (CYP3A4 and CYP2D6 inhibition), Echinacea (presystemic/hepatic CYP3A4 inhibition/induction, CYP1A2 and CYP2C9 inhibition at high doses). Information was found not always complete for the major drug metabolizing CYP enzymes in the less well-studied herbs and is largely limited to P-glycoprotein (ABCB1) when effects on drug transporters have been investigated.

 
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