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SHORT COMMUNICATION

MULTIPLE NIGHT-TIME DOSES OF VALERIAN (Valeriana officinalis) HAD MINIMAL EFFECTS ON CYP3A4 ACTIVITY AND NO EFFECT ON CYP2D6 ACTIVITY IN HEALTHY VOLUNTEERS

Laboratory of Drug Disposition and Pharmacogenetics, Departments of Pharmaceutical Sciences (J.S.M.), Psychiatry and Behavioral Sciences (J.L.D., C.L.D., J.S.W., B.B.G., H.A.G.), and Surgery (K.D.C.), Medical University of South Carolina, Charleston, South Carolina

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 C_max, 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.

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