title: Drug cocktail interaction study on the effect of the orally administered lavender oil preparation silexan on cytochrome P450 enzymes in healthy volunteers.
abstract: This cocktail study evaluated the interaction potential of the oral lavender oil preparation silexan with major P450 (cytochrome P450) enzymes.
  
  
  METHODS
  Sixteen healthy male or female Caucasians completed this double-blind, randomized, 2-fold crossover study. Silexan (160 mg) or placebo were administered once daily for 11 days. Additionally, on day 11 of both study periods, 150 mg caffeine (CYP1A2), 125 mg tolbutamide (CYP2C9), 20 mg omeprazole (CYP2C19), 30 mg dextromethorphan-HBr (CYP2D6), and 2 mg midazolam (CYP3A4) were administered orally. Formal interaction was excluded if the 90% confidence interval (CI) for the silexan over placebo ratios for phenotyping metrics (primary: AUC(0-t)) was within a 0.70-1.43 range.
  
  
  RESULTS
  According to the AUC(0-t) comparisons, silexan had no relevant effect on CYP1A2, 2C9, 2D6, and 3A4 activity. Secondary phenotyping metrics confirmed this result. Mean ratios for all omeprazole-derived metrics were close to unity. The 90% CI for the AUC(0-t) ratio of omeprazole but not for omeprazole/5-OH-omeprazole plasma ratio 3 hours post-dose or omeprazole/5-OH-omeprazole AUC(0-t) ratio (secondary CYP2C19 metrics) was above the predefined threshold of 1.43, probably caused by the inherent high variability of omeprazole pharmacokinetics. Silexan and the phenotyping drugs were well tolerated. Repeated silexan (160 mg/day) administration has no clinically relevant inhibitory or inducing effects on the CYP1A2, 2C9, 2C19, 2D6, and 3A4 enzymes in vivo.
authors: ITECRA GmbH & Co. KG, Cologne, Germany.
authors: Oxana
authors: O
authors: Doroshyenko
authors: Dennis
authors: D
authors: Rokitta
authors: Gregor
authors: G
authors: Zadoyan
authors: Stephan
authors: S
authors: Klement
authors: Sandra
authors: S
authors: Schläfke
authors: Angelika
authors: A
authors: Dienel
authors: Thomas
authors: T
authors: Gramatté
authors: Hendrik
authors: H
authors: Lück
authors: Uwe
authors: U
authors: Fuhr
mesh_terms: D000080462:Acyclic Monoterpenes; D000284:Administration, Oral; D019540:Area Under Curve; D018592:Cross-Over Studies; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects*; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D006801:Humans; D027523:Lavandula; D057230:Limit of Detection; D008297:Male; D039821:Monoterpenes / Q000097:blood; D009822:Oils, Volatile / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D010919:Placebos; D010938:Plant Oils / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D000080462:Acyclic Monoterpenes; D039821:Monoterpenes; D009822:Oils, Volatile; D010919:Placebos; D010938:Plant Oils; C074463:linalyl acetate; D003577:Cytochrome P-450 Enzyme System; C018584:linalool; C045718:lavender oil