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Drug Metabolism and Disposition Fast Forward
First published on August 24, 2004; DOI: 10.1124/dmd.104.001164

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Received for publication June 24, 2004.
Revised August 19, 2004.
Accepted for publication August 23, 2004.

Multiple Nighttime Doses of Valerian (Valeriana officinalis) had Minimal Effects on CYP 3A4 activity and No Effect on CYP 2D6 Activity in Healthy Volunteers

Jennifer L Donovan 1, C. Lindsay DeVane 1, Kenneth D Chavin 1, Jun-Sheng Wang 1, Bryan B Gibson 1, Holly A Gefroh 1, John S Markowitz 2*

1 Medical University of South Carolina 2 Medical University of South carolina

* Address correspondence to: E-mail: markowij{at}musc.edu

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 P- 450 (CYP) 2D6 and 3A4. Probe drugs dextromethorphan (DM, 30mg, CYP2D6 activity) and alprazolam (ALPZ, 2mg, CYP3A4 activity) were administered orally to healthy volunteers (n =12) at baseline, and again following 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 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 540 ± 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 Cmax, Valerian, taken at typical doses is unlikely to produce clinically significant effects on the disposition of medications dependent on the CYP2D6 or CYP3A4 pathways of metabolism.


Key words: bioavailability, CYP2D, CYP3A, drug interactions, pharmacokinetics


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