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 > or = 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 hx ng x 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.
Laboratory of Drug Disposition and Pharmacogenetics, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
Jennifer L
JL
Donovan
C Lindsay
CL
DeVane
Kenneth D
KD
Chavin
Jun-Sheng
JS
Wang
Bryan B
BB
Gibson
Holly A
HA
Gefroh
John S
JS
Markowitz
D000328:Adult; D000525:Alprazolam / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism*; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003915:Dextromethorphan / Q000493:pharmacokinetics; D003917:Dextrorphan / Q000493:pharmacokinetics; D004347:Drug Interactions; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D004364:Pharmaceutical Preparations / Q000378:metabolism; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology; D014632:Valerian / Q000737:chemistry*
D004364:Pharmaceutical Preparations; D010936:Plant Extracts; D003917:Dextrorphan; D003915:Dextromethorphan; D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; D019389:Cytochrome P-450 CYP2D6; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D000525:Alprazolam