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Multiple doses of saw palmetto ( Serenoa repens ) did not alter cytochrome P450 2D6 and 3A4 activity in normal volunteers
Author(s) -
Markowitz John S.,
Donovan Jennifer L.,
DeVane C. Lindsay,
Taylor Robin M.,
Ruan Ying,
Wang JunSheng,
Chavin Kenneth D.
Publication year - 2003
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.2003.08.010
Subject(s) - dextromethorphan , alprazolam , pharmacology , cyp2d6 , cyp3a4 , pharmacokinetics , medicine , metabolite , dextrorphan , cytochrome p450 , metabolism , anxiety , psychiatry
Saw palmetto ( Serenoa repens ) is the most commonly used herbal preparation in the treatment of benign prostatic hyperplasia. The objective of this study was to determine whether a characterized saw palmetto product affects the activity of cytochrome P450 (CYP) 2D6 or 3A4 in healthy volunteers (6 men and 6 women). The probe substrates dextromethorphan (CYP2D6 activity) and alprazolam (CYP3A4 activity) were administered orally at baseline and again after exposure to saw palmetto (320‐mg capsule once daily) for 14 days. Dextromethorphan metabolic ratios and alprazolam pharmacokinetics were determined at baseline and after saw palmetto treatment. The mean ratio of dextromethorphan to its metabolite was 0.038 ± 0.044 at baseline and 0.048 ± 0.080 after 14 days of saw palmetto administration ( P = .704, not significant [NS]), indicating a lack of effect on CYP2D6 activity. The area underthe plasma alprazolam concentration versus time curve was 476 ± 178 h · ng · mL −1 at baseline and 479 ± 125 h · ng · mL −1 after saw palmetto treatment ( P = .923, NS), indicating a lack of effect on CYP3A4 activity. The elimination half‐life of alprazolam was 11.4± 3.1 hours at baseline and 11.6 ± 2.7 hours after saw palmetto treatment ( P = .770, NS), also indicating a lack of effect on CYP3A4 activity. Our results indicate that extracts of saw palmetto at generally recommended doses are unlikely to alter the disposition of coadministered medications primarily dependent on the CYP2D6 or CYP3A4 pathways for elimination. These conclusions must be weighed in the context of the study's limited assessments and regarded as only the initial investigation into the drug interaction potential of saw palmetto. Clinical Pharmacology & Therapeutics (2003) 74 , 536–542; doi: 10.1016/j.clpt.2003.08.010