Effects of St. John's Wort (Hypericum perforatum) on tacrolimus pharmacokinetics in healthy volunteers

Tacrolimus is an immunosuppressant approved for the prevention of rejection following transplantation and is a substrate for CYP3A and P-glycoprotein. A pharmacokinetic interaction between St. John's wort (antidepressant herbal product and inducer of CYP3A and P-glycoprotein) and tacrolimus was evaluated in 10 healthy volunteers. The pharmacokinetics of tacrolimus were obtained from serial blood samples collected following single oral doses (0.1 mg/kg) prior to and during an 18-day concomitant St. John's wort dosing phase (300 mg orally three times daily). Coadministration of St. John's wort significantly decreased tacrolimus AUC(306,9 mug(.)h/L+/-175.8mug(.)h/L vs. 198.7 mug(.)h/L +/- 139.6 mug(.)h/L; p = 0.004) and increased apparent oral clearance (349.0 mL/h/kg +/-126.0 mL/h/kg vs. 586.4 mL/h/kg +/- 274.9 mL/h/kg; p = 0.01) and apparent oral volume of distribution at steady state (11.5 L/kg +/- 4.3 L/kg vs. 17.6 L/kg +/- 9.6 L/kg, p = 0.04). St. John's wort appears to induce tacrolimus metabolism, most likely through induction of GYP3A and P-glycoprotein. (C) 2004 the American College of Clinical Pharmacology.