¹Department of Pharmaceutical Sciences, Department of Psychiatry and Behavioral Sciences, and Department of Surgery, Division of Transplantation, Medical University of South Carolina, Charleston, SC, USA

Correspondence: John S. Markowitz, PharmD, Medical University of South Carolina, Institute of Psychiatry, RM 246 North, Laboratory of Drug Disposition and Pharmacogenetics, 67 President St, Charleston, SC 29425, USA. E-mail: markowij@musc.edu

^*This publication was made possible by grant No. R21 AT00511 from the National Center for Complementary and Alternative Medicine (NCCAM). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Center for Complementary and Alternative Medicine, National Institutes of Health. United States Public Health Service grant No. M01 RR01070-18 provided funding of the clinical study at the Medical University of South Carolina General Clinical Research Center.

Received 4 June 2003; Accepted 28 August 2003.

Abstract

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.