Drug cocktail interaction study on the effect of the orally administered lavender oil preparation silexan on cytochrome p450 enzymes in healthy volunteers

Drug Metabolism and Disposition

Volumn 41, Issue 5, 2013, Pages 987-993

  Doroshyenko, Oxana ^a   Rokitta, Dennis ^b   Zadoyan, Gregor ^a,b   Klement, Stephan ^c   Schläfke, Sandra ^c   Dienel, Angelika ^c   Gramatté, Thomas ^d   Lück, Hendrik ^a   Fuhr, Uwe ^a,b  

^a ITECRA GmbH and Co KG   (Germany)

^b UNIVERSITY OF COLOGNE   (Germany)

^c DR WILLMAR SCHWABE GMBH AND CO KG   (Germany)

^d Drug Development Consulting   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

5 HYDROXYOMEPRAZOLE; CAFFEINE; CYTOCHROME P450; CYTOCHROME P450 1A2; CYTOCHROME P450 2C19; CYTOCHROME P450 2C9; CYTOCHROME P450 2D6; CYTOCHROME P450 3A4; DEXTROMETHORPHAN; DORMICUM V; DRUG METABOLITE; LAVENDER OIL; MIDAZOLAM; OMEPRAZOLE; PLACEBO; SILEXAN; TOLBUTAMIDE; UNCLASSIFIED DRUG;

ADULT; AREA UNDER THE CURVE; ARTICLE; CAUCASIAN; COMMON COLD; CONTROLLED STUDY; CROSSOVER PROCEDURE; DIARRHEA; DIZZINESS; DOUBLE BLIND PROCEDURE; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG ELIMINATION; DRUG HALF LIFE; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; ENZYME ACTIVITY; ERUCTATION; ERYTHROCYTE COUNT; FEMALE; HEMATOCRIT; HUMAN; HUMAN EXPERIMENT; IN VIVO STUDY; MALE; MAXIMUM PLASMA CONCENTRATION; NAUSEA; NORMAL HUMAN; PHENOTYPE; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SIDE EFFECT; TIME TO MAXIMUM PLASMA CONCENTRATION; VOLUNTEER; VOMITING;

ADMINISTRATION, ORAL; AREA UNDER CURVE; CROSS-OVER STUDIES; CYTOCHROME P-450 ENZYME SYSTEM; DOUBLE-BLIND METHOD; DRUG INTERACTIONS; FEMALE; HUMANS; LIMIT OF DETECTION; MALE; MONOTERPENES; OILS, VOLATILE; PLACEBOS; PLANT OILS;

LAVANDULA;

EID: 84876762702     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.112.050203     Document Type: Article

References (38)

1. Adedoyin A, Frye RF, Mauro K, and Branch RA (1998) Chloroquine modulation of specific metabolizing enzymes activities: Investigation with selective five drug cocktail. Br J Clin Pharmacol 46:215-219.
2. Andersson T, Bergstrand R, and Cederberg C (1991) Influence of acid secretory status on absorption of omeprazole from enteric coated granules. Br J Clin Pharmacol 31:275-278.
3. Andersson T, Miners JO, Veronese ME, Tassaneeyakul W, Tassaneeyakul W, Meyer UA, and Birkett DJ (1993) Identification of human liver cytochrome P450 isoforms mediating omeprazole metabolism. Br J Clin Pharmacol 36:521-530.
4. Chang M, Dahl M-L, Tybring G, Götharson E, and Bertilsson L (1995) Use of omeprazole as a probe drug for CYP2C19 phenotype in Swedish Caucasians: Comparison with S-mephenytoin hydroxylation phenotype and CYP2C19 genotype. Pharmacogenetics 5:358-363.
5. Christensen M, Andersson K, Dalén P, Mirghani RA, Muirhead GJ, Nordmark A, Tybring G, Wahlberg A, Yaşar U, and Bertilsson L (2003) The Karolinska cocktail for phenotyping of five human cytochrome P450 enzymes. Clin Pharmacol Ther 73:517-528.
6. Council of Europe (2008) European pharmacopoeia 6.0, Lavender oil (Lavandulae aetheroleum) monograph 01/2008:1338, European directorate for the quality of medicines and health care, p. 2244-2245
7. European Medicines Agency (2012a) Community herbal monograph on Lavandula angustifolia Miller, flos, EMA/HMPC/734125/2010, March 27, 2012, Committee on Herbal Medicinal Products.
8. European Medicines Agency (2012b) Community herbal monograph on Lavandula angustifolia Miller, aetheroleum EMA/HMPC/143181/2010, March 27, 2012, Committee on Herbal Medicinal Products.
9. European Medicines Agency (2012c): Guideline on the Investigation of Drug Interactions CPMP/ EWP/560/95/Rev. 1, June 21, 2012, Committee for Human Medicinal Products.
10. Endres HG, Henschel L, Merkel U, Hippius M, and Hoffmann A (1996) Lack of pharmacokinetic interaction between dextromethorphan, coumarin and mephenytoin in man after simultaneous administration. Pharmazie 51:46-51.
11. Food and Drug Administration (2012) Guidance for Industry. Drug Interaction Studies-Study Design, Data Analysis, Implications for Dosing, and Labeling Recommendations. Draft Guidance, February 2012, Center for Drug Evaluation and Research.
12. Frank D, Jaehde U, and Fuhr U (2007) Evaluation of probe drugs and pharmacokinetic metrics for CYP2D6 phenotyping. Eur J Clin Pharmacol 63:321-333.
13. Frye RF, Matzke GR, Adedoyin A, Porter JA, and Branch RA (1997) Validation of the five-drug "Pittsburgh cocktail" approach for assessment of selective regulation of drug-metabolizing enzymes. Clin Pharmacol Ther 62:365-376.
14. Fuhr U, Jetter A, and Kirchheiner J (2007) Appropriate phenotyping procedures for drug metabolizing enzymes and transporters in humans and their simultaneous use in the "cocktail" approach. Clin Pharmacol Ther 81:270-283.
15. Gorski JC, Huang SM, Pinto A, Hamman MA, Hilligoss JK, Zaheer NA, Desai M, Miller M, and Hall SD (2004) The effect of echinacea (Echinacea purpurea root) on cytochrome P450 activity in vivo. Clin Pharmacol Ther 75:89-100.
16. Howden CW, Meredith PA, Forrest JA, and Reid JL (1984) Oral pharmacokinetics of omeprazole. Eur J Clin Pharmacol 26:641-643.
17. Jetter A, Kinzig-Schippers M, Skott A, Lazar A, Tomalik-Scharte D, Kirchheiner J, Walchner-Bonjean M, Hering U, Jakob V, and Rodamer M, et al. (2004) Cytochrome P450 2C9 phenotyping using low-dose tolbutamide. Eur J Clin Pharmacol 60:165-171.
18. Kasel D, Harlfinger S, Kinzig-Schippers M, Soergel F, Gebhardt W, and Fuhr U (2002) Determination of midazolam in human plasma using LC-MS/MS devices from two different manufacturers. Eur J Clin Pharmacol 58:87.
19. Kasper S, Gastpar M, Müller WE, Volz HP, Möller HJ, Dienel A, and Schläfke S (2010b) Efficacy and safety of silexan, a new, orally administered lavender oil preparation, in subthreshold anxiety disorder-evidence from clinical trials. Wien Med Wochenschr 160:547-556.
20. Kasper S, Gastpar M, Müller WE, Volz HP, Möller HJ, Dienel A, and Schläfke S (2010a) Silexan, an orally administered Lavandula oil preparation, is effective in the treatment of 'subsyndromal' anxiety disorder: A randomized, double-blind, placebo controlled trial. Int Clin Psychopharmacol 25:277-287.
21. Klaassen T, Jetter A, Tomalik-Scharte D, Kasel D, Kirchheiner J, Jaehde U, and Fuhr U (2008) Assessment of urinary mephenytoin metrics to phenotype for CYP2C19 and CYP2B6 activity. Eur J Clin Pharmacol 64:387-398.
22. NN (2008) Summary of product characteristics for Omeprazol-Ratiopharm NT 20 mg hard capsule as of June 2008, Ratiopharm GmbH, Neu-Ulm, Germany.
23. NN (2010) Summary of product characteristics for LASEA 80 mg soft capsule as of September 2010, W. Spitzner Arzneimittelfabrik GmbH, Ettlingen, Germany.
24. NN (2012) Summary of product characteristics for omeprazole 20 mg capsules as of August 29, 2012, Actavis UK Ltd, Whiddon Valley, Barnstaple, Devon, UK.
25. Rani S and Pargal S (2004) Bioequivalence: An overview of statistical concepts. Indian J Pharmacol 36:209-216.
26. Roh H-K, Dahl M-L, Tybring G, Yamada H, Cha Y-N, and Bertilsson L (1996) CYP2C19 genotype and phenotype determined by omeprazole in a Korean population. Pharmacogenetics 6:547-551.
27. Sharma A, Pilote S, Bélanger PM, Arsenault M, and Hamelin BA (2004) A convenient five-drug cocktail for the assessment of major drug metabolizing enzymes: A pilot study. Br J Clin Pharmacol 58:288-297.
28. Schellens JH, van der Wart JH, Brugman M, and Breimer DD (1989) Influence of enzyme induction and inhibition on the oxidation of nifedipine, sparteine, mephenytoin and antipyrine in humans as assessed by a "cocktail" study design. J Pharmacol Exp Ther 249:638-645.
29. Steinijans VW, Hartmann M, Huber R, and Radtke HW (1996) Lack of pharmacokinetic interaction as an equivalence problem. Int J Clin Pharmacol Ther 34(1, Suppl)S25-S30.
30. Streetman DS, Bertino JS, Jr, and Nafziger AN (2000) Phenotyping of drug-metabolizing enzymes in adults: A review of in-vivo cytochrome P450 phenotyping probes. Pharmacogenetics 10:187-216.
31. Tomalik-Scharte D, Jetter A, Kinzig-Schippers M, Skott A, Sörgel F, Klaassen T, Kasel D, Harlfinger S, Doroshyenko O, and Frank D, et al. (2005) Effect of propiverine on cytochrome P450 enzymes: A cocktail interaction study in healthy volunteers. Drug Metab Dispos 33: 1859-1866.
32. Tucker GT, Houston JB, and Huang SM (2001) Optimizing drug development: Strategies to assess drug metabolism/transporter interaction potential-towards a consensus. Br J Clin Pharmacol 52:107-117.
33. Turpault S, Brian W, Van Horn R, Santoni A, Poitiers F, Donazzolo Y, and Boulenc X (2009) Pharmacokinetic assessment of a five-probe cocktail for CYPs 1A2, 2C9, 2C19, 2D6 and 3A. Br J Clin Pharmacol 68:928-935.
34. Wang Z, Gorski JC, Hamman MA, Huang SM, Lesko LJ, and Hall SD (2001) The effects of St John's wort (Hypericum perforatum) on human cytochrome P450 activity. Clin Pharmacol Ther 70:317-326.
35. Woelk H and Schläfke S (2010) A multi-center, double-blind, randomised study of the Lavender oil preparation Silexan in comparison to Lorazepam for generalized anxiety disorder. Phytomedicine 17:94-99.
36. Wohlfarth A, Naue J, Lutz-Bonengel S, Dresen S, and Auwärter V (2012) Cocktail approach for in vivo phenotyping of 5 major CYP450 isoenzymes: Development of an effective sampling, extraction, and analytical procedure and pilot study with comparative genotyping. J Clin Pharmacol 52:1200-1214.
37. Zadoyan G, Rokitta D, Klement S, Dienel A, Hoerr R, Gramatté T, and Fuhr U (2012) Effect of Ginkgo biloba special extract EGb 761® on human cytochrome P450 activity: A cocktail interaction study in healthy volunteers. Eur J Clin Pharmacol 68:553-560.
38. Zhu B, Ou-Yang DS, Chen XP, Huang SL, Tan ZR, He N, and Zhou HH (2001) Assessment of cytochrome P450 activity by a five-drug cocktail approach. Clin Pharmacol Ther 70:455-461.