Abstract
Valerian (Valeriana officinalis) is a popular dietary supplement. The objective of this study was to assess the influence of a valerian extract on the activity of the drug-metabolizing enzymes cytochrome P450 2D6 (CYP2D6) and 3A4. Probe drugs dextromethorphan (30 mg; CYP2D6 activity) and alprazolam (2 mg; CYP3A4 activity) were administered orally to healthy volunteers (n = 12) at baseline and again after exposure to two 500-mg valerian tablets (1000 mg) nightly for 14 days. The valerian supplement contained a total valerenic acid content of 5.51 mg/tablet. Dextromethorphan to dextorphan metabolic ratios (DMRs) and alprazolam pharmacokinetics were determined at baseline and after valerian treatment. The DMR was 0.214 ± 0.025 at baseline and 0.254 ± 0.026 after valerian supplementation (p > 0.05). For alprazolam, the maximum concentration in plasma was significantly increased after treatment with valerian (25 ± 7 ng/ml versus 31 ± 8 ng/ml; p < 0.05). There were no significant differences in other pharmacokinetic parameters at baseline and after valerian exposure (all p values ≥0.05; time to reach maximum concentration in plasma, 3.0 ± 3.2 versus 3.1 ± 2.1 h; area under the plasma concentration versus time curve, 471 ± 183 versus 539 ± 240 h · ng · ml-1; half-life of elimination, 13.5 ± 4.3 versus 12.2 ± 5.6 h). Our results indicate that although a modest increase was observed in the alprazolam Cmax, typical doses of valerian are unlikely to produce clinically significant effects on the disposition of medications dependent on the CYP2D6 or CYP3A4 pathways of metabolism.
Footnotes
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This study was made possible by Grant R21 AT00511 from the National Center for Complementary and Alternative Medicine. 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. Furthermore, the authors gratefully acknowledge Public Health Service Grant M01 RR01070-18 for the funding of the clinical study at the Medical University of South Carolina General Clinical Research Center.
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doi:10.1124/dmd.104.001164.
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ABBREVIATIONS: P450, cytochrome P450; ALPZ, alprazolam; AUC, area under the time versus concentration curve; Cmax, maximum concentration in plasma; DM, dextromethorphan; DMR, dextromethorphan to dextorphan metabolic ratio; Tmax, time to reach maximum concentration in plasma; GCRC, General Clinical Research Center.
- Received June 23, 2004.
- Accepted August 23, 2004.
- The American Society for Pharmacology and Experimental Therapeutics
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