To evaluate the hypothesis that Hypericum perforatum enhances P-glycoprotein activity, researchers in the USA conducted a study in 12 healthy volunteers using fexofenadine as a marker of P-glycoprotein activity. The volunteers received oral fexofenadine, 60 mg, prior to receiving H. perforatum, with a single dose of oral H. perforatum 900 mg, and after receiving H. perforatum 300 mg three times daily with food for 14–15 days. Blood and urine samples were taken at intervals up to 48 h after each dose of fexofenadine. A single dose of H. perforatum resulted in a significant 45% increase in the maximum plasma concentration (C_max) of fexofenadine and a 20% decrease in oral clearance, with no change in half-life, time to reach C_max or renal clearance. Long-term administration of H. perforatum did not result in significant changes in oral clearance or C_max compared with values prior to treatment. However, the researchers did note a significant decrease in the renal excretion of fexofenadine after long-term, but not after single-dose, administration of H. perforatum.