Elderly patients are more likely to ingest prescription medications concurrently with botanical supplements, therefore, they may be vulnerable to herb-drug interactions. Phytochemical-mediated modulation of cytochrome P-450 (CYP) activity may underlie many herb-drug interactions. Some evidence suggests that CYP activity may decrease in the elderly. If so, herb-mediated changes in CYP activity may take on greater clinical relevance in this population. Single time-point, phenotypic metabolic ratios were used to determine whether long-term supplementation of St. John’s wort, garlic oil, Panax ginseng, and Ginkgo biloba affected CYP1A2, CYP2D6, CYP2E1, or CYP3A4 activity in elderly subjects.
Twelve healthy volunteers between the ages of 60 and 76 (mean = 67 years) were randomly assigned to receive each supplement for 28 days followed by a 30-day washout period. Probe drug cocktails of midazolam, caffeine, chlorzoxazone, and debrisoquine were administered before and at the end of supplementation. Pre- and postsupplementation phenotypic ratios were determined for CYP3A4, CYP1A2, CYP2E1, and CYP2D6 using 1-hydroxymidazolam/midazolam serum ratios (1-hr), paraxanthine/caffeine serum ratios (6-hr), 6-hydroxychlorzoxazone/chlorzoxazone serum ratios (2-hr), and debrisoquine urinary recovery ratios (8-hr), respectively. The content of purported “active” phytochemicals was determined for each supplement.
Comparisons of pre- and post-St. John’s wort phenotypic ratios revealed significant induction of CYP3A4 (~140%) and CYP2E1 activity (~28%). Garlic oil inhibited CYP2E1 activity by approximately 22%. P. ginseng inhibition of CYP2D6 was statistically significant, but the magnitude of the effect (~7%) did not appear clinically relevant. None of the supplements tested in this study appeared to affect CYP1A2 activity.
Elderly subjects, like their younger counterparts, are susceptible to herb-mediated changes in CYP activity, especially those involving St. John’s wort. Pharmacokinetic herb-drug interactions stemming from alterations in CYP activity may adversely affect drug efficacy and/or toxicity. When compared to earlier studies that employed young subjects, the data suggest that some age-related changes in CYP responsivity to botanical supplementation may exist. Concomitant ingestion of botanical supplements with prescription medications, therefore, should be strongly discouraged in the elderly.