Effects of St. John's Wort (Hypericum Perforatum) On the Oral Pharmacokinetics of Tacrolimus in Health Volunteers
St. John's wort is an over the counter alternative medicine used for
depression. Previous studies using
6-hydroxycortisol:cortisol
ratio as
an enzyme marker, suggest it is an inducer of the enzyme CYP3A. Previous
interactions with digoxin suggest it is also an inducer of P-glycoprotein
(P-gp).
Tacrolimus is an immunosupressant used for the prevention of rejection in transplant recipients. Tacrolimus is a substrate for CYP3A and P-gp. CYP3A metabolizes tacrolimus making it more water soluble by adding water soluble side chains which enhance its elimination via the kidney or through the bile. The pharmacokinetics of tacrolimus are affected by various inducers and inhibitors of CYP3A and/or P-gp.
Concominant use of St. John's wort is anticipated to decrease blood concentrations of tacrolimus, potentially resulting in allograft rejection in transplant recipients.
Previous studies of CYP3A activity was measured only before and after a two week exposure to St. John's wort. This study will assess daily changes in CYP3A activity before, during, and after St. John's wort administration by measuring 6<\beta>-hydroxycortisol:cortisol ratio in subjects first morning urine. Cortisol is a steroid which normally exists in the body. 6<\beta>-hydroxycortisol is a metabolite of cortisol. A change in the ratio of 6<\beta>-hydroxycortisol to cortisol suggests that St. John's wort is inducing the enzyme CYP3A.
The purpose of this study is to determine if St. John's wort coadministration affects the ability of the human body to handle tacrolimus after oral administration.
