Planta Med 2012; 78 - PH10
DOI: 10.1055/s-0032-1320669

Herb-Drug Interactions: Effects of Echinacea preparations on cytochrome P450 activities in rats

K Ardjomand-Woelkart 1, M Kollroser 2, H Derendorf 3, R Bauer 1, V Butterweck 3, 4
  • 1Institute of Pharmaceutical Sciences, Department of Pharmacognosy, Karl-Franzens-University Graz, 8010 Graz, Austria
  • 2Institute of Forensic Medicine, Medical University of Graz, 8010 Graz, Austria
  • 3Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville FL 32610, USA
  • 4University of Applied Sciences, School of Life Sciences, Institute for Pharma Technology, 4132 Muttenz, Switzerland

Different preparations of Echinacea angustifolia DC., Echinacea purpurea (L.) Moench and Echinacea pallida (Nutt.) Nutt. were investigated for its cytochrome P450 (CYP) interaction potential in rats. Rats were assigned to the different study groups with various dosages, positive controls (ketoconazole, quinidine), or pure compounds (dodeca-2E,4E,8Z,10E/Z-tetraenoic acid isobutylamides; tetraenes). After pretreatment with the different Echinacea preparations for 14 days, a cocktail of probe drugs for CYP enzymes (theophylline [CYP1A2], tolbutamide [CYP2C9], dextromethorphan [CYP2D6] and midazolam [CYP3A4]) was orally administered before blood sampling. Plasma levels of probe drugs and their metabolites were quantified using a validated LC-MS/MS method before and 0.25, 0.5, 1, 2, 4, 6, 10 and 24h after a single dose of the probe cocktail. Pharmacokinetic parameters (Cmax, AUClast) were calculated and compared with the control group using geometric mean ratio (GMR) and its 90% confidence interval (CI). Some E. purpurea preparations showed significant inhibitions in CYP1A2 activities. In addition, the tetraenes inhibited CYP1A2 with a GMR of 8.65 (7.72–9.68) for the AUClast and 2.96 (2.59–3.39) for Cmax. Echinacea preparations showed no inhibition in CYP3A4 and CYP2C9, and only a moderate or weak inhibition in CYP2D6 activities.