Integrating Pharmacogenetics for Assessment of Herb-Drug Interactions: Has the Time Come?

It is increasingly common for patients to use western medications concurrently with Traditional Chinese Medicine or other herbal medicines. Indeed, it is estimated that one-third of people in developed countries are using alternative therapies including herbal medicines. Metabolism of drugs/herbs takes place to a large extent in the liver and small intestine via various drug-metabolizing enzymes. Therefore, the concurrent use of western and herbal medicines has potential for drug-herb interactions at these biological locations. There are several hepatic metabolic enzymes and drug transporters that have been documented to be involved in the herb-drug interactions. These include the cytochrome P450 (CYP450) enzymes that contribute to metabolism of various drugs, food constituents, and herbs, and the ATPbinding cassette (ABC) transporters, particularly P-glycoprotein (P-gp), and solute carrier (SLC) transporters. Pharmacogenetic variance in CYP450s and drug transporters in humans and animals may lead to pharmacokinetic and pharmacodynamics changes of target substrates which could be drugs and/or herbal medicines. This paper presents a synthesis of the emerging evidence on the role of pharmacogenetics in the mechanism of the salient herb-drug interactions, and why the time has come to consider integrating this new strand of postgenomics knowledge to clinical and public health practice.