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Multiple Night-Time Doses of Valerian Had Minimal Effects on CYP3A4 Activity and No Effect on CYP2D6

Multiple Night-Time Doses of Valerian Had Minimal Effects on CYP3A4 Activity and No Effect on CYP2D6

  1. Jatelka
    Drug Metabolism and Disposition. 32:1333–1336, 2004

    JENNIFER L. DONOVAN C. LINDSAY DEVANE KENNETH D. CHAVIN JUN-SHENG WANG BRYAN B. GIBSON HOLLY A. GEFROH JOHN S. MARKOWITZ

    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 Valerian (Valeriana officinalis) extracts are marketed as dietary supplements in the United States and were among the top 10 bestselling herbal supplements in the United States in 2002 (Blumenthal, 2003). Although they are currently promoted as a sedative/hypnotic, clinical trials are presently inconclusive with regard to the efficacy for insomnia (Houghton, 1999; Stevinson and Ernst, 2000; Krystal and Ressler, 2001). Valerian supplements contain a complex mixture of chemical constituents (Shohet et al., 2001). The main constituents are valerenic acid and its derivatives contained in the volatile oil (Houghton, 1999). These main constituents are widely thought to contribute to the putative sedative effects, although clinical effects may be a result of synergistic activity from numerous constituents. The valepotriates have also been investigated for pharmacologic activity but are relatively unstable and are often not present in most commercial supplements (Bos et al., 2002). Minor constituents include various alkaloids, furanofuran lignans, and free amino acids (Houghton, 1999). Valerian 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 ml1; 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 signifi-cant effects on the disposition of medications dependent on the CYP2D6 or CYP3A4 pathways of metabolism.