RT Journal Article
SR Electronic
T1 Drug Cocktail Interaction Study on the Effect of the Orally Administered Lavender Oil Preparation Silexan on Cytochrome P450 Enzymes in Healthy Volunteers
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 987
OP 993
DO 10.1124/dmd.112.050203
VO 41
IS 5
A1 Oxana Doroshyenko
A1 Dennis Rokitta
A1 Gregor Zadoyan
A1 Stephan Klement
A1 Sandra Schläfke
A1 Angelika Dienel
A1 Thomas Gramatté
A1 Hendrik Lück
A1 Uwe Fuhr
YR 2013
UL http://dmd.aspetjournals.org/content/41/5/987.abstract
AB This cocktail study evaluated the interaction potential of the oral lavender oil preparation silexan with major P450 (cytochrome P450) enzymes. Subjects and 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: AUC0–t) was within a 0.70–1.43 range. Results: According to the AUC0–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 AUC0–t ratio of omeprazole but not for omeprazole/5-OH-omeprazole plasma ratio 3 hours post-dose or omeprazole/5-OH-omeprazole AUC0–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.