The effect of echinacea (500 mg three times daily for two weeks) on the pharmacokinetics of lopinavir/ritonavir (400/100 mg twice daily) was studied in 13 HIV- subjects. Neither lopinavir nor ritonavir pharmacokinetics were altered by coadministration of echinacea (lopinavir AUC decreased by 4% and there was no change in Cmax), most likely due to the presence of the potent CYP3A inhibitor, ritonavir. Echinacea purpurea is unlikely to alter the pharmacokinetics of ritonavir-boosted protease inhibitors but may cause modest decreases in plasma concentrations of other CYP3A substrates.

The effect of echinacea on CYP activity was assessed by use of a number of CYP probe drugs (caffeine for CYP1A2; tolbutamide for CYP2C9; dextromethorphan for CYP2D6 and midazolam for both hepatic and intestinal CYP3A) in a study in 12 healthy volunteers. The data demonstrated that echinacea caused inhibition of CYP1A2 and intestinal CYP3A activity and induction of hepatic CYP3A activity. The authors indicate that for CYP3A substrates (such as protease inhibitors), the type of drug interaction observed with echinacea will be dependent on the relative extraction of the drugs at hepatic and intestinal sites and will not be readily predicted. Certainly echinacea could contribute to inter-patient variability in protease inhibitor levels.