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Effect of botanical supplementation on cytochrome P450 phenotypes in the elderly
Author(s) -
Gurley B.J.,
Gardner S.F.,
Hubbard M.A.,
Williams D.K.,
Gentry W.B.
Publication year - 2005
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2004.11.063
Subject(s) - chlorzoxazone , paraxanthine , cyp1a2 , caffeine , debrisoquine , cyp2d6 , pharmacology , ginseng , medicine , cyp3a4 , traditional medicine , ginkgo biloba , pharmacokinetics , chemistry , cytochrome p450 , cyp2e1 , metabolism , alternative medicine , pathology
Background Herb‐drug interactions may be of particular concern in the elderly. Single time‐point, phenotypic metabolic ratios were used to determine whether supplementation of Ginkgo biloba, Panax ginseng, garlic oil, or St. John's wort extracts affected CYP1A2, CYP2D6, CYP2E1, or CYP3A4 activity in elderly subjects. Methods Twelve healthy volunteers between the ages of 60 and 76 (mean= 66 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 post‐supplementation 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. Results 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 (~22%). Ginseng inhibited CYP2D6, but the magnitude (~7%) did not appear clinically relevant. CYP1A2 activity in the elderly was unaffected by herb supplementation. Conclusions Elderly subjects, like their younger counterparts, are susceptible to herb‐mediated changes in CYP activity, especially those involving St. John's wort. Clinical Pharmacology & Therapeutics (2005) 77 , P16–P16; doi: 10.1016/j.clpt.2004.11.063