Drug cocktail interaction study on the effect of the orally administered lavender oil preparation silexan on cytochrome P450 enzymes in healthy volunteers
| Autor: | G Zadoyan, Thomas Gramatté, Dennis Rokitta, Angelika Dienel, Oxana Doroshyenko, Sandra Schläfke, Uwe Fuhr, Hendrik Lück, Stephan Klement |
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| Rok vydání: | 2013 |
| Předmět: |
Male
CYP2D6 Acyclic Monoterpenes Pharmaceutical Science Administration Oral Lavender oil CYP2C19 Pharmacology Placebo Placebos Pharmacokinetics Cytochrome P-450 Enzyme System Double-Blind Method Limit of Detection medicine Oils Volatile Humans Plant Oils Drug Interactions Omeprazole Cross-Over Studies Chemistry Crossover study Lavandula Area Under Curve Monoterpenes Midazolam Female medicine.drug |
| Zdroj: | Drug metabolism and disposition: the biological fate of chemicals. 41(5) |
| ISSN: | 1521-009X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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