Multiple night-time doses of valerian (Valeriana officinalis) had minimal effects on CYP3A4 activity and no effect on CYP2D6 activity in healthy volunteers

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.