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 microg.h/L +/- 175.8 microg.h/L vs. 198.7 microg.h/L +/- 139.6 microg.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.
Hebert
Mary F
MF
University of Washington, Department of Pharmacy, Seattle, WA 98195-7630, USA.
Park
Jeong M
JM
Chen
Yu-Luan
YL
Akhtar
Shahzad
S
Larson
Anne M
AM
D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D004347:Drug Interactions; D005260:Female; D006207:Half-Life; D006801:Humans; D020902:Hypericum; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D016559:Tacrolimus / Q000097:blood / Q000493:pharmacokinetics*
D007166:Immunosuppressive Agents; D016559:Tacrolimus