Background: St. John's wort (SJW) is a popular over-the-counter herbal remedy that has been implicated in drug interactions with several substrates of p-glycoprotein. The effect of SJW on p-glycoprotein activity in vivo was examined using fexofenadine as selective probe drug.
Methods: A three period, open-label, fixed schedule study design was employed. Fexofenadine, 60 mg, was administered orally before SJW dosing, with acute SJW dosing (900 mg), and after two weeks of SJW (300 mg tid) intake to determine p-glycoprotein activity.
Results: Acute administration of SJW significantly increased the Cmax and AUC of fexofenadine by 1.4- and 1.3-fold, respectively but did not alter the half-life or renal clearance. Chronic SJW administration caused a nonsignificant 0.85-fold decrease in fexofenadine AUC and Cmax relative to the untreated phase with no change in half-life or renal clearance of fexofenadine. When compared to the acute treatment phase, chronic SJW caused a significant decreases in fexofenadine AUC and Cmax of 0.66- and 0.62-fold and respectively.
Conclusion: Acute dosing of SJW administration resulted in an inhibition of intestinal p-glycoprotein and an elevated AUC of fexofenadine. Chronic SJW treatment reversed the inhibition seen on acute dosing and resulted in enhancement of intestinal p-glycoprotein activity and reduced AUC of fexofenadine.
Acknowledgement: FDA grant#FD-T-001756-01; the authors acknowledge the contribution of Drs. Jerry Collins and Peter Honig