Trial Information

Effects of Ginseng and Ginkgo on Drug Disposition in Man

Over 60 million Americans use herbal medicines; of these, one-fourth also take prescription
drugs. Physicians are often unaware of herbal use and of possible drug/herb interactions in
their patients. Ginseng and ginkgo, enhancers of physical and mental performance, are two of
the most widely taken herbals. We propose a double-blind, randomized, prospective study of
effects of ginseng and ginkgo on 1) disposition of probe drugs, 2) cognitive function, and
3) glutathione-S-transferase (GST) and quinone reductase (NQ01), enzymes implicated in
chemoprevention of cancer. Probe drugs will be administered to study effects of herbs on
their disposition, not for therapeutic effect. Ideal probes must be safe, well tolerated,
have minimal pharmacological effect, and share known metabolic pathways with other
clinically used drugs. Medically stable drug-free non-smokers will be enrolled.

During a 4-week single-blind run-in, subjects will be given a 4-drug probe cocktail:
caffeine to study cytochrome P4501A2 (CYP1A2), dextromethorphan for CYP2D6, buspirone (and
endogenous cortisol) for CHP3A and fexofenadine for P-glycoprotein. Losartan will be given
separately for CYP2C9. These enzymes metabolize over 95% of clinically used drugs. Enzyme
activities will be determined by assaying appropriate blood and urine specimens for probe
drugs and metabolites. Cognitive function will be tested and blood lymphocytes collected for
measuring GST and NQ01 activities. Sixty subjects will then be randomly assigned to one of 4
double-blind treatment groups of 15 each: 1) ginseng extract (Ginsana), 2) ginkgo extract
(Egb761), 3) both herbs, or 4) matching placebos. Tolerability of herbs will be determined.
After 6 to 8 weeks of twice daily treatment with study agents, all effect parameters will
be reevaluated: probe drug pharmacokinetics, cognitive function, and GST and NQ01 in blood
lymphocytes. Interactions of chronic ginseng and ginkgo with drug-metabolizing pathways and
with cognitive function will thus be determined.