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Effects of St. John's Wort (Hypericum perforatum) on Tacrolimus Pharmacokinetics in Healthy Volunteers

From the University of Washington, Departments of Pharmacy (Dr. Hebert, Dr. Park) and Medicine (Dr. Larson), Seattle, Washington, and Fujisawa Research Institute of America, Evanston, Illinois (Dr. Chen, Dr. Akhtar).

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 µg•h/L ± 175.8 µg•h/L vs. 198.7 µg•h/L ± 139.6 µg•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 CYP3A and P-glycoprotein.

Key Words: St. John's wort • tacrolimus • organ transplantation • depression

Address for reprints: Mary F. Hebert, PharmD, University of Washington, Department of Pharmacy, H-375 Health Sciences Center, Box 357630, Seattle, WA 98195-7630.