Reverse Herbology: Predicting and Preventing Adverse Herb-Drug Interactions

Steven A. Kliewer, Ph.D.
Departments of Molecular Biology and Pharmacology
University of Texas Southwestern Medical Center at Dallas

There is a growing awareness that herbs can adversely affect the clinical efficacy of prescription drugs, sometimes with life-threatening consequences. A notable example is the herbal antidepressant St. John's wort, which promotes the metabolism of many drugs including the immunosuppressant cyclosporin, the HIV protease inhibitors indinavir and nevirapine, the cancer drug irinotecan, the anticoagulant warfarin, and oral contraceptives. Co-administration of St. John's wort with these drugs can reduce their concentrations to dangerously low levels. The molecular basis for this type of herb-drug interaction is now understood: St. John's wort activates a receptor, named PXR, in the liver and intestine, which accelerates drug metabolism. This lecture will present recent findings regarding activation of PXR by St. John's wort and other herbs and discuss how this knowledge can be applied to predict and prevent harmful interactions between herbs and prescription drugs.