Title:Herb-Drug Interactions and Mechanistic and Clinical Considerations
VOLUME: 13 ISSUE: 5
Author(s):Xiao-Wu Chen, Kevin B. Sneed, Si-Yuan Pan, Chuanhai Cao, Jagat R. Kanwar, Helen Chew and Shu- Feng Zhou
Affiliation:Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, 12901 Bruce B. Downs Blvd., MDC 30, Tampa, Florida 33612, USA.
Keywords:Herb medicine, drug interaction, toxicity, pharmacokinetics, CYP, P-gp, Interactions, Herbal medicines, conventional drugs, cytochrome P450s, P-glycoprotein, Toxicity, Ginkgo biloba, St John’s wort, ethnic groups
Abstract:Herbal medicines are often used in combination with conventional drugs, and this may give rise to the potential of harmful
herb-drug interactions. This paper updates our knowledge on clinical herb-drug interactions with an emphasis of the mechanistic and
clinical consideration. In silico, in vitro, animal and human studies are often used to predict and/or identify drug interactions with herbal
remedies. To date, a number of clinically important herb-drug interactions have been reported, but many of them are from case reports
and limited clinical observations. Common herbal medicines that interact with drugs include St John’s wort (Hypericum perforatum),
ginkgo (Ginkgo biloba), ginger (Zingiber officinale), ginseng (Panax ginseng), and garlic (Allium sativum). For example, St John's wort
significantly reduced the area under the plasma concentration-time curve (AUC) and blood concentrations of cyclosporine, midazolam,
tacrolimus, amitriptyline, digoxin, indinavir, warfarin, phenprocoumon and theophylline. The common drugs that interact with herbal
medicines include warfarin, midazolam, digoxin, amitriptyline, indinavir, cyclosporine, tacrolimus and irinotecan. Herbal medicines may
interact with drugs at the intestine, liver, kidneys, and targets of action. Importantly, many of these drugs have very narrow therapeutic
indices. Most of them are substrates for cytochrome P450s (CYPs) and/or P-glycoprotein (P-gp). The underlying mechanisms for most
reported herb-drug interactions are not fully understood, and pharmacokinetic and/or pharmacodynamic mechanisms are implicated in
many of these interactions. In particular, enzyme induction and inhibition may play an important role in the occurrence of some herbdrug
interactions. Because herb-drug interactions can significantly affect circulating levels of drug and, hence, alter the clinical outcome,
the identification of herb-drug interactions has important implications.