Potential for interaction of kava and St. 's wort with drugs

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J Ethnopharmacol. 2005 Aug 22;100(1-2):108-13.

Potential for interaction of kava and St. 's wort with drugs.

Singh YN.

College of Pharmacy, South Dakota State University, Brookings, SD

57007, USA.

The present interest and widespread use of herbal remedies has

created the possibility of interaction between them and

pharmaceutical drugs if they are used simultaneously. Before the

recent reports of apparent hepatotoxicity associated with its use,

kava (Piper methysticum Forst. F.), was one of the top 10 selling

herbal remedies in Europe and North America. This adverse effect was

not previously encountered with the traditional beverage which was

prepared as a water infusion in contrast to the commercial products

which are extracted with organic solvents. Kavalactones, the active

principles in kava, are potent inhibitors of several of the CYP 450

enzymes, suggesting a high potential for causing pharmacokinetic

interactions with drugs and other herbs which are metabolized by the

same CYP 450 enzymes. Furthermore, some kavalactones have been shown

to possess pharmacological effects, such as blockade of GABA

receptors and sodium and calcium ion channels, which may lead to

pharmacodynamic interactions with other substances which possess

similar pharmacological proprieties. St. 's wort (Hypericum

perforatum L.), used extensively for the treatment of mild to

moderate clinical depression, has long been considered safer than the

conventional pharmaceutical agents. However, its ability, through its

active constituents hypericin, pseudohypericin and hyperforin, to

induce intestinal P-glycoprotein/MRD1 and both intestinal and hepatic

CYP3A4 enzyme, could markedly reduce the distribution and disposition

of their co-substrates. In addition, St. 's wort is a potent

uptake inhibitor of the neurotransmitters serotonin, norepinephrine

and dopamine all of which have a role in mood control. Consequently,

the very real potential for a pharmacodynamic interaction between the

herb and pharmaceutical drugs which share this mechanism of action

and, like St. 's wort, are used for mood elevation. However,

presently there is very little evidence to substantiate actual

pharmacokinetic and/or pharmacodynamic interaction between drugs and

kava or St. 's wort. This review provides a brief overview of the

existing data on interactions of kava and St. 's wort with

pharmaceutical agents and as a result reveals the urgent need for

detailed investigations to identify clinically significant

interactions for these herbal remedies that have the potential to

cause adverse effects.