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.