Botanical-drug interaction mechanisms

While defining the overall pharmacokinetic or pharmacodynamic basis of botanical-drug interactions may be relatively straightforward, attempts to explain the underlying mechanism of altered drug concentrations or to predict the magnitude and significance of the interaction is certainly not easy. There are several factors that contribute to this difficulty, and they are briefly discussed below. 

CYP enzymes are induced, resulting in reduced plasma drug levels. Alternatively, CYP enzymes could also undergo mechanism-based inhibition, whereby a CYP enzyme can be completely inactivated by covalent bonding to a component of the herb. Furthermore, botanicals can elicit a biphasic cellular response, whereby CYP activity may be inhibited initially, followed by induction after prolonged incubation or repeated administration. Such factors would need to be considered in future studies in order to establish the true risk of ginseng in herb-drug interactions. 

While theoretically it is possible that botanicals with diuretic effects can increase drug excretion, most botanical diuretics are not as potent as furo-semide and are unlikely to result in significant interactions. Most botanicals also do not affect urinary pH significantly, and hence are unlikely to affect renal tubular reabsorption of drugs. Nevertheless, lithium toxicity was thought to be related to the use of a botanical diuretic mixture in a patient. If the toxicity indeed is related to the use of the botanical diuretic, the mechanism of action or the responsible constituent(s) is not known (48). 

Although most botanical products are probably safe under most conditions, some are known to be toxic at high doses and others may have potentially adverse effects under some conditions. Many dangerous and lethal side effects have been reported from the use of herbal products. These side effects may occur through several different mechanisms, including direct toxic effects of the herb, effects of contaminants, and interactions with drugs or other herbs. 

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